{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:30:53Z","timestamp":1784259053346,"version":"3.55.0"},"reference-count":268,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T00:00:00Z","timestamp":1574035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is a mounting cause of loss of sight in the elderly in the developed countries, a trend enhanced by the continual ageing of the population. AMD is a multifactorial and only partly understood, malady. Unfortunately, there is no effective treatment for most AMD patients. It is known that oxidative stress (OS) damages the retinal pigment epithelium (RPE) and contributes to the progression of AMD. We review here the potential importance of two OS-related cellular systems in relation to AMD. First, the nuclear factor erythroid 2-related factor 2 (NFE2L2; NRF2)-mediated OS response signalling pathway is important in the prevention of oxidative damage and a failure of this system could be critical in the development of AMD. Second, epithelial-to-mesenchymal transition (EMT) represents a change in the cellular phenotype, which ultimately leads to the fibrosis encountered in RPE, a characteristic of AMD. Many of the pathways triggering EMT are promoted by OS. The possible interconnections between these two signalling routes are discussed here. From a broader perspective, the control of NFE2L2 and EMT as ways of preventing OS-derived cellular damage could be potentially valuable in the therapy of AMD.<\/jats:p>","DOI":"10.3390\/ijms20225800","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T11:18:48Z","timestamp":1574075928000},"page":"5800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology"],"prefix":"10.3390","volume":"20","author":[{"given":"Juha M. T.","family":"Hyttinen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Kannan","sequence":"additional","affiliation":[{"name":"The Stephen J. Ryan Initiative for Macular Research (RIMR), Doheny Eye Institute, DVRC 203, 1355 San Pablo Street, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs","family":"Felszeghy","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"},{"name":"Institute of Dentistry, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"Niittykoski","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antero","family":"Salminen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kaarniranta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland"},{"name":"Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, 70029 KYS Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neuron.2012.06.018","article-title":"Mechanisms of age-related macular degeneration","volume":"75","author":"Ambati","year":"2012","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e305","DOI":"10.2741\/1019","article-title":"Age-related macular degeneration: A new viewpoint","volume":"8","author":"Hamdi","year":"2003","journal-title":"Front. Biosci."},{"key":"ref_3","unstructured":"United Nations, Department of Economic and Social Affairs, Population Division (2013). World Population Prospects: The 2012 Revision, Highlights and Advance Tables, United Nations, Department of Economic and Social Affairs, Population. Working paper no. ESA\/P\/WP.228."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_5","unstructured":"National Guideline Alliance (2018). Age-Related Macular Degeneration: Diagnosis and Management, National Guideline Alliance. National Institute for Health and Care Excellence: Clinical Guidelines."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Winkler, T.W., Brandl, C., Grassmann, F., Gorski, M., Stark, K., Loss, J., Weber, B.H.F., and Heid, I.M. (2018). International Age-related Macular Degeneration Genomics Consortium (IAMDGC). Investigating the modulation of genetic effects on late AMD by age and sex: Lessons learned and two additional loci. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194321"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1038\/s41433-018-0044-0","article-title":"What do we know about the macular pigment in AMD: The past, the present, and the future","volume":"32","author":"Arunkumar","year":"2018","journal-title":"Eye"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7619","DOI":"10.1167\/iovs.14-14471","article-title":"Lifetime exposure to ambient ultraviolet radiation and the risk for cataract extraction and age-related macular degeneration: The Alienor Study","volume":"55","author":"Delcourt","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhou, H., Zhang, H., Yu, A., and Xie, J. (2018). Association between sunlight exposure and risk of age-related macular degeneration: A meta-analysis. BMC Ophthalmol., 18.","DOI":"10.1186\/s12886-018-1004-y"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"ORSF68","DOI":"10.1167\/iovs.13-12757","article-title":"Dry age-related macular degeneration: Mechanisms, therapeutic targets, and imaging","volume":"54","author":"Farsiu","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1096\/fj.14-262444","article-title":"Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage","volume":"29","author":"Jobling","year":"2015","journal-title":"FASEB J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.1167\/iovs.13-11993","article-title":"Fight Retinal Blindness! Project Investigators. Prospective audit of exudative age-related macular degeneration: 12-month outcomes in treatment-naive eyes","volume":"54","author":"Gillies","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev-vision-111815-114407","article-title":"Retinoids and retinal diseases","volume":"2","author":"Kiser","year":"2016","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/B978-0-12-394309-5.00004-3","article-title":"Mechanisms for countering oxidative stress and damage in retinal pigment epithelium","volume":"298","author":"Plafker","year":"2012","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.1097\/IAE.0000000000001325","article-title":"Hyperspectral autofluorescence imaging of drusen and retinal pigment epithelium in donor eyes with age-related macular degeneration","volume":"36","author":"Tong","year":"2016","journal-title":"Retina"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1167\/iovs.07-1466","article-title":"Prevalence and morphology of druse types in the macula and periphery of eyes with age-related maculopathy","volume":"49","author":"Rudolf","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/aos.13011","article-title":"Drusen maculopathy: A risk factor for visual deterioration","volume":"94","author":"Algvere","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.12688\/f1000research.10664.1","article-title":"Recent advances in the management of dry age-related macular degeneration: A review","volume":"6","author":"Bandello","year":"2017","journal-title":"F1000Research"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.mam.2012.04.005","article-title":"Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor\/retinal pigment epithelium\/Bruch\u2019s membrane\/choriocapillaris complex","volume":"33","author":"Bhutto","year":"2012","journal-title":"Mol. Aspects Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.exer.2010.02.013","article-title":"Macromolecular diffusion characteristics of ageing human Bruch\u2019s membrane: Implications for age-related macular degeneration (AMD)","volume":"90","author":"Hussain","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_22","first-page":"8125267","article-title":"Choriocapillaris loss in advanced age-related macular degeneration","volume":"2018","author":"Moult","year":"2018","journal-title":"J. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.preteyeres.2017.06.005","article-title":"Fluorescence lifetime imaging ophthalmoscopy","volume":"60","author":"Dysli","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.1167\/iovs.14-14802","article-title":"Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium","volume":"55","author":"Ach","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.2741\/e198","article-title":"Mechanisms of protein aggregation in the retinal pigment epithelial cells","volume":"2","author":"Kaarniranta","year":"2010","journal-title":"Front. Biosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.mam.2012.03.006","article-title":"How does the macula protect itself from oxidative stress?","volume":"33","author":"Handa","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Roehlecke, C., Schumann, U., Ader, M., Brunssen, C., Bramke, S., Morawietz, H., and Funk, R.H. (2013). Stress reaction in outer segments of photoreceptors after blue light irradiation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071570"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.arr.2017.03.006","article-title":"DNA damage response and autophagy in the degeneration of retinal pigment epithelial cells\u2014Implications for age-related macular degeneration (AMD)","volume":"36","author":"Hyttinen","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2119\/molmed.2010.00070","article-title":"Endoplasmic reticulum stress in age-related macular degeneration: Trigger for neovascularization","volume":"16","author":"Salminen","year":"2010","journal-title":"Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.exer.2014.01.016","article-title":"Studying melanin and lipofuscin in RPE cell culture models","volume":"126","author":"Boulton","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/978-3-319-17121-0_8","article-title":"Extracellular matrix alterations and deposit formation in AMD","volume":"854","author":"Pierce","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.arr.2014.07.002","article-title":"Clearance of misfolded and aggregated proteins by aggrephagy and implications for aggregation diseases","volume":"18","author":"Hyttinen","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1007\/s00018-016-2147-8","article-title":"Inflammation and its role in age-related macular degeneration","volume":"73","author":"Kauppinen","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1755-148X.2007.00432.x","article-title":"Correlation between melanogenic and catalase activity in in vitro human melanocytes: A synergic strategy against oxidative stress","volume":"21","author":"Maresca","year":"2008","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1016\/j.yexcr.2012.05.019","article-title":"Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis","volume":"318","author":"Cunha","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1751-1097.1987.tb05362.x","article-title":"Photoinduced generation of hydrogen peroxide and hydroxyl radicals in melanins","volume":"45","author":"Korytowski","year":"1987","journal-title":"Photochem. Photobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000336777","article-title":"Oxidation levels differentially impact melanocytes: Low versus high concentration of hydrogen peroxide promotes melanin synthesis and melanosome transfer","volume":"224","author":"Tang","year":"2012","journal-title":"Dermatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.micron.2015.08.001","article-title":"Ultrastructural changes in the melanocytes of aging human choroid","volume":"79","author":"Nag","year":"2015","journal-title":"Micron"},{"key":"ref_39","first-page":"768026","article-title":"Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration","volume":"2014","author":"Petrovski","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Chen, Y., Wang, J., Sternberg, P., Freeman, M.L., Grossniklaus, H.E., and Cai, J. (2011). Age-related retinopathy in NRF2-deficient mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019456"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.redox.2018.09.011","article-title":"Loss of NRF-2- and PGC-1\u03b1 genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration","volume":"20","author":"Felszeghy","year":"2018","journal-title":"Redox Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.exer.2015.03.009","article-title":"Molecular mechanisms of subretinal fibrosis in age-related macular degeneration","volume":"142","author":"Ishikawa","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1016\/j.bbagen.2013.04.006","article-title":"Punctum on two different transcription factors regulated by PGC-1\u03b1: Nuclear factor erythroid-derived 2-like 2 and nuclear respiratory factor 2","volume":"1830","author":"Baldelli","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.arr.2018.06.003","article-title":"Nrf2: Molecular and epigenetic regulation during aging","volume":"47","author":"Zazueta","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1006\/bbrc.1995.1467","article-title":"cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription factor","volume":"209","author":"Chui","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1006\/bbrc.1997.6943","article-title":"An Nrf2\/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements","volume":"236","author":"Itoh","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.abb.2016.10.010","article-title":"Keap1 as the redox sensor of the antioxidant response","volume":"617","author":"Sihvola","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.freeradbiomed.2015.06.006","article-title":"Molecular basis of the Keap1-Nrf2 system","volume":"88 Pt B","author":"Suzuki","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","first-page":"19","article-title":"The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders","volume":"6","author":"Gao","year":"2014","journal-title":"Clin. Pharmacol."},{"key":"ref_50","first-page":"1503","article-title":"Loss of Nrf2 exacerbates the visual deficits and optic neuritis elicited by experimental autoimmune encephalomyelitis","volume":"22","author":"Larabee","year":"2016","journal-title":"Mol. Vis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/icb\/icq034","article-title":"Nrf2, a guardian of healthspan and gatekeeper of species longevity","volume":"50","author":"Lewis","year":"2010","journal-title":"Integr. Comp. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7469326","DOI":"10.1155\/2016\/7469326","article-title":"Nrf2 is an attractive therapeutic target for retinal diseases","volume":"2016","author":"Nakagami","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/dvg.22964","article-title":"Broad-complex, tramtrack, and bric-\u00e0-brac (BTB) proteins: Critical regulators of development","volume":"54","author":"Chaharbakhshi","year":"2016","journal-title":"Genesis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.freeradbiomed.2005.01.021","article-title":"Redox regulation of the transcriptional repressor Bach1","volume":"38","author":"Ishikawa","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-1119(02)00788-6","article-title":"Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors","volume":"294","author":"Motohashi","year":"2002","journal-title":"Gene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1074\/jbc.RA117.000428","article-title":"Kelch-like ECH-associated protein 1 (KEAP1) differentially regulates nuclear factor erythroid-2-related factors 1 and 2 (NRF1 and NRF2)","volume":"293","author":"Tian","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/onc.2012.59","article-title":"The nuclear cofactor RAC3\/AIB1\/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains","volume":"32","author":"Kim","year":"2013","journal-title":"Oncogene"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/03602532.2016.1197239","article-title":"Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters","volume":"48","author":"Bai","year":"2016","journal-title":"Drug Metab. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/BJ20150568","article-title":"KEAP1-NRF2 signalling and autophagy in protection against oxidative and reductive proteotoxicity","volume":"469","author":"Dodson","year":"2015","journal-title":"Biochem. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7629","DOI":"10.1074\/jbc.M110.208173","article-title":"Acetylation-deacetylation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) regulates its transcriptional activity and nucleocytoplasmic localization","volume":"286","author":"Kawai","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_61","first-page":"556","article-title":"Mazes of Nrf2 regulation","volume":"82","author":"Zenkov","year":"2017","journal-title":"Biochemistry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.taap.2004.08.023","article-title":"Toxicity and detoxification of lipid-derived aldehydes in cultured retinal pigmented epithelial cells","volume":"204","author":"Choudhary","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/978-1-4614-3209-8_38","article-title":"A mechanistic review of cigarette smoke and age-related macular degeneration","volume":"801","author":"Woodell","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"C1200","DOI":"10.1152\/ajpcell.00126.2009","article-title":"Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: Implications for age-related macular degeneration","volume":"297","author":"Bertram","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1042\/BST20150069","article-title":"The Keap1\/Nrf2 pathway in health and disease: From the bench to the clinic","volume":"43","author":"Hayes","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1021\/acs.jafc.7b01929","article-title":"Lutein activates the transcription factor Nrf2 in human retinal pigment epithelial cells","volume":"65","author":"Frede","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_67","first-page":"760","article-title":"Pinosylvin-mediated protection against oxidative stress in human retinal pigment epithelial cells","volume":"20","author":"Koskela","year":"2014","journal-title":"Mol. Vis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1007\/s00018-016-2223-0","article-title":"Role of Nrf2\/HO-1 system in development, oxidative stress response and diseases: An evolutionarily conserved mechanism","volume":"73","author":"Loboda","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.yexmp.2016.07.008","article-title":"The influence of changes in expression of redox-sensitive genes on the development of retinopathy in rats","volume":"101","author":"Perepechaeva","year":"2016","journal-title":"Exp. Mol. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.redox.2018.05.002","article-title":"Antioxidant response elements: Discovery, classes, regulation and potential applications","volume":"17","author":"Raghunath","year":"2018","journal-title":"Redox Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1006\/bbrc.2001.5944","article-title":"Functional characterization of transcription regulators that interact with the electrophile response element","volume":"289","author":"Zhu","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"De los Fayos Alonso, I.G., Liang, H.C., Turner, S.D., Lagger, S., Merkel, O., and Kenner, L. (2018). The role of activator protein-1 (AP-1) family members in CD30-positive lymphomas. Cancers, 10.","DOI":"10.3390\/cancers10040093"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/jcb.25619","article-title":"Specificity of stress-responsive transcription factors Nrf2, ATF4, and AP-1","volume":"118","author":"Thiel","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1101\/gad.13.1.76","article-title":"Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain","volume":"13","author":"Itoh","year":"1999","journal-title":"Genes Dev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1128\/MCB.26.8.2887-2900.2006","article-title":"Keap1 recruits Neh2 through binding to ETGE and DLG motifs: Characterization of the two-site molecular recognition model","volume":"26","author":"Tong","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1128\/MCB.26.4.1235-1244.2006","article-title":"CAND1-mediated substrate adaptor recycling is required for efficient repression of Nrf2 by Keap1","volume":"26","author":"Lo","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1128\/MCB.00389-16","article-title":"Absolute amounts and status of the Nrf2-Keap1-Cul3 complex within cells","volume":"36","author":"Iso","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1021\/tx0502138","article-title":"Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane","volume":"18","author":"Hong","year":"2005","journal-title":"Chem. Res. Toxicol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1128\/MCB.25.1.162-171.2005","article-title":"BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase","volume":"25","author":"Furukawa","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"10941","DOI":"10.1128\/MCB.24.24.10941-10953.2004","article-title":"Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex","volume":"24","author":"Zhang","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"21592","DOI":"10.1074\/jbc.M300931200","article-title":"Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression","volume":"278","author":"McMahon","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e00660-16","DOI":"10.1128\/MCB.00660-16","article-title":"p97 negatively regulates NRF2 by extracting ubiquitylated NRF2 from the KEAP1-CUL3 E3 complex","volume":"37","author":"Tao","year":"2017","journal-title":"Mol. Cell. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"11908","DOI":"10.1073\/pnas.172398899","article-title":"Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants","volume":"99","author":"Holtzclaw","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1128\/MCB.00868-15","article-title":"Characterizations of three major cysteine sensors of Keap1 in stress response","volume":"36","author":"Saito","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8137","DOI":"10.1128\/MCB.23.22.8137-8151.2003","article-title":"Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress","volume":"23","author":"Zhang","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1021\/tx700302s","article-title":"Covalent modification at Cys151 dissociates the electrophile sensor Keap1 from the ubiquitin ligase CUL3","volume":"21","author":"Rachakonda","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_87","first-page":"32","article-title":"Oxidative damage and age-related macular degeneration","volume":"5","author":"Winkler","year":"1999","journal-title":"Mol. Vis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.freeradbiomed.2012.06.023","article-title":"Validation of the multiple sensor mechanism of the Keap1-Nrf2 system","volume":"53","author":"Takaya","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1089\/ars.2017.7290","article-title":"The role of sirtuins in antioxidant and redox signaling","volume":"28","author":"Singh","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.yexcr.2017.09.042","article-title":"The crosstalk between Sirt1 and Keap1\/Nrf2\/ARE anti-oxidative pathway forms a positive feedback loop to inhibit FN and TGF-\u03b21 expressions in rat glomerular mesangial cells","volume":"361","author":"Huang","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"42769","DOI":"10.1074\/jbc.M206911200","article-title":"Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription","volume":"277","author":"Huang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1128\/MCB.00118-16","article-title":"AMPK facilitates nuclear accumulation of Nrf2 by phosphorylating at Serine 550","volume":"36","author":"Joo","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"C334","DOI":"10.1152\/ajpcell.00043.2003","article-title":"Atypical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress","volume":"285","author":"Numazawa","year":"2003","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.phrs.2018.06.013","article-title":"Canonical and non-canonical mechanisms of Nrf2 activation","volume":"134","author":"Maldonado","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8984","DOI":"10.1074\/jbc.M709040200","article-title":"Multiple nuclear localization signals function in the nuclear import of the transcription factor Nrf2","volume":"283","author":"Theodore","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"27251","DOI":"10.1074\/jbc.M602746200","article-title":"Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain","volume":"281","author":"Li","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/j.bbamcr.2008.05.024","article-title":"Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif","volume":"1783","author":"Li","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s00125-017-4523-9","article-title":"Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function","volume":"61","author":"He","year":"2018","journal-title":"Diabetologia"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1128\/MCB.01639-08","article-title":"Acetylation of Nrf2 by p300\/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response","volume":"29","author":"Sun","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.tox.2017.06.006","article-title":"The electrophilic character of quinones is essential for the suppression of Bach1","volume":"387","author":"Su","year":"2017","journal-title":"Toxicology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/iub.314","article-title":"C-Myc is a Nrf2-interacting protein that negatively regulates phase II genes through their electrophile responsive elements","volume":"62","author":"Levy","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.freeradbiomed.2019.01.028","article-title":"Does Bach1 & c-Myc dependent redox dysregulation of Nrf2 & adaptive homeostasis decrease cancer risk in ageing?","volume":"134","author":"Davies","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"11632","DOI":"10.1016\/S0021-9258(18)99004-6","article-title":"The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity","volume":"266","author":"Rushmore","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1073\/pnas.94.10.5361","article-title":"Functional antioxidant responsive elements","volume":"94","author":"Wasserman","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1423-0127-16-12","article-title":"Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells","volume":"16","author":"Hsieh","year":"2009","journal-title":"J. Biomed. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1089\/10445490360708883","article-title":"Nrf2 regulates thromboxane synthase gene expression in human lung cells","volume":"22","author":"Yaekashiwa","year":"2003","journal-title":"DNA Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1759091415593294","DOI":"10.1177\/1759091415593294","article-title":"Nrf2 and HSF-1 pathway activation via hydroquinone-based proelectrophilic small molecules is regulated by electrochemical oxidation potential","volume":"7","author":"Satoh","year":"2015","journal-title":"ASN Neuro"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1124\/mol.109.058453","article-title":"NRF2 cysteine residues are critical for oxidant\/electrophile-sensing, Kelch-like ECH-associated protein-1-dependent ubiquitination-proteasomal degradation, and transcription activation","volume":"76","author":"He","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1016\/j.neurobiolaging.2014.01.143","article-title":"Primary cultured astrocytes from old rats are capable to activate the Nrf2 response against MPP+ toxicity after tBHQ pretreatment","volume":"35","author":"Lazzarini","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1128\/MCB.00785-15","article-title":"The mediator subunit MED16 transduces NRF2-activating signals into antioxidant gene expression","volume":"36","author":"Sekine","year":"2015","journal-title":"Mol. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1111\/bph.12661","article-title":"The histone acetyltranseferase hMOF acetylates Nrf2 and regulates anti-drug responses in human non-small cell lung cancer","volume":"171","author":"Chen","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"10895","DOI":"10.1128\/MCB.25.24.10895-10906.2005","article-title":"The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation","volume":"25","author":"Nioi","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6334","DOI":"10.1128\/MCB.00630-07","article-title":"Keap1 controls postinduction repression of the Nrf2-mediated antioxidant response by escorting nuclear export of Nrf2","volume":"27","author":"Sun","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/MCO.0b013e32834136f2","article-title":"The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic regulation","volume":"14","author":"Sykiotis","year":"2011","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.bbamcr.2014.05.003","article-title":"Modulation of NRF2 signaling pathway by nuclear receptors: Implications for cancer","volume":"1843","author":"Namani","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.cell.2016.06.056","article-title":"NRF2 promotes tumor maintenance by modulating mRNA translation in pancreatic cancer","volume":"166","author":"Chio","year":"2016","journal-title":"Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1158\/2159-8290.CD-16-0127","article-title":"Role of KEAP1\/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiation resistance","volume":"7","author":"Jeong","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/hep.27790","article-title":"Nrf2, but not \u03b2-catenin, mutation represents an early event in rat hepatocarcinogenesis","volume":"62","author":"Zavattari","year":"2015","journal-title":"Hepatology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.freeradbiomed.2011.01.033","article-title":"Molecular cross-talk between the NRF2\/KEAP1 signaling pathway, autophagy, and apoptosis","volume":"50","author":"Kruszewski","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.freeradbiomed.2015.06.014","article-title":"p62 links autophagy and Nrf2 signaling","volume":"88 Pt B","author":"Jiang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.molcel.2009.04.029","article-title":"Direct interaction between Nrf2 and p21(Cip1\/WAF1) upregulates the Nrf2-mediated antioxidant response","volume":"34","author":"Chen","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"16782","DOI":"10.1074\/jbc.M109.096545","article-title":"Physical and functional interaction of sequestosome 1 with Keap1 regulates the Keap1-Nrf2 cell defense pathway","volume":"285","author":"Copple","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"22576","DOI":"10.1074\/jbc.M110.118976","article-title":"p62\/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription","volume":"285","author":"Jain","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/ncb2021","article-title":"The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1","volume":"12","author":"Komatsu","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1128\/MCB.00248-10","article-title":"A noncanonical mechanism of Nrf2 activation by autophagy deficiency: Direct interaction between Keap1 and p62","volume":"30","author":"Lau","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.bbrc.2015.09.059","article-title":"PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1","volume":"466","author":"Park","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_127","first-page":"M43","article-title":"p21(WAF1\/Cip1): More than a break to the cell cycle?","volume":"1471","author":"Dotto","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.redox.2015.11.011","article-title":"Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for age-related macular degeneration","volume":"7","author":"Marazita","year":"2016","journal-title":"Redox Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1038\/onc.2012.388","article-title":"Nrf2 is controlled by two distinct \u03b2-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity","volume":"32","author":"Chowdhry","year":"2013","journal-title":"Oncogene"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1089\/ars.2017.7084","article-title":"Oxidative Stress induces an interactive decline in Wnt and Nrf2 signaling in degenerating retinal pigment epithelium","volume":"29","author":"Ebrahimi","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1158\/0008-5472.CAN-07-2170","article-title":"Activating transcription factor 3 is a novel repressor of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-regulated stress pathway","volume":"68","author":"Brown","year":"2008","journal-title":"Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"39776","DOI":"10.1074\/jbc.M605707200","article-title":"p53 suppresses the Nrf2-dependent transcription of antioxidant response genes","volume":"281","author":"Faraonio","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.mce.2007.08.011","article-title":"ERR\u03b2: A potent inhibitor of Nrf2 transcriptional activity","volume":"278","author":"Zhou","year":"2007","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1128\/MCB.25.10.4150-4165.2005","article-title":"Glucocorticoid receptor (GR)-associated SMRT binding to C\/EBP\u03b2 TAD and Nrf2 Neh4\/5: Role of SMRT recruited to GR in GSTA2 gene repression","volume":"25","author":"Ki","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","article-title":"Nrf2-Keap1 signaling in oxidative and reductive stress","volume":"1865","author":"Bellezza","year":"2018","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev.immunol.021908.132641","article-title":"Regulation and function of NF-kappaB transcription factors in the immune system","volume":"27","author":"Vallabhapurapu","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev-biochem-061516-045037","article-title":"Oxidative stress","volume":"86","author":"Sies","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"15244","DOI":"10.1074\/jbc.M113.540633","article-title":"Transcription factors NRF2 and NF-\u03baB are coordinated effectors of the Rho family, GTP-binding protein RAC1 during inflammation","volume":"289","author":"Cuadrado","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.freeradbiomed.2011.12.006","article-title":"Histone deacetylase inhibition activates transcription factor Nrf2 and protects against cerebral ischemic damage","volume":"52","author":"Wang","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.exger.2009.09.002","article-title":"NF-kappaB signaling as a putative target for omega-3 metabolites in the prevention of age-related macular degeneration (AMD)","volume":"44","author":"Kaarniranta","year":"2009","journal-title":"Exp. Gerontol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.phrs.2011.05.027","article-title":"Celastrol regulates innate immunity response via NF-\u03baB and Hsp70 in human retinal pigment epithelial cells","volume":"64","author":"Paimela","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.preteyeres.2016.08.001","article-title":"Autophagy in the eye: Development, degeneration, and aging","volume":"55","author":"Boya","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.bbamcr.2008.07.014","article-title":"Autophagy: A lysosomal degradation pathway with a central role in health and disease","volume":"1793","author":"Eskelinen","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.tcb.2016.03.006","article-title":"Digesting the expanding mechanisms of autophagy","volume":"26","author":"Ktistakis","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the pathogenesis of disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1101\/gad.1599207","article-title":"Autophagy: Process and function","volume":"21","author":"Mizushima","year":"2007","journal-title":"Genes Dev."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.exer.2015.11.007","article-title":"Aberrant protein trafficking in retinal degenerations: The initial phase of retinal remodeling","volume":"150","author":"Bales","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10565-016-9371-8","article-title":"Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration","volume":"33","author":"Kaarniranta","year":"2017","journal-title":"Cell. Biol. Toxicol."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Keeling, E., Lotery, A.J., Tumbarello, D.A., and Ratnayaka, J.A. (2018). Impaired cargo clearance in the retinal pigment epithelium (RPE) underlies irreversible blinding diseases. Cells, 7.","DOI":"10.20944\/preprints201801.0269.v1"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1152\/physiolgenomics.00041.2017","article-title":"Nrf2 at the heart of oxidative stress and cardiac protection","volume":"50","author":"Chen","year":"2018","journal-title":"Physiol. Genom."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1080\/15548627.2015.1061170","article-title":"The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells","volume":"11","author":"Johansson","year":"2015","journal-title":"Autophagy"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Darvekar, S.R., Elvenes, J., Brenne, H.B., Johansen, T., and Sj\u00f8ttem, E. (2014). SPBP is a sulforaphane induced transcriptional coactivator of NRF2 regulating expression of the autophagy receptor p62\/SQSTM1. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085262"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/ars.2015.6549","article-title":"Repurposing the NRF2 activator dimethyl fumarate as therapy against synucleinopathy in Parkinson\u2019s disease","volume":"25","author":"Scannevin","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/j.febslet.2014.04.046","article-title":"Targeting Nrf2 by dihydro-CDDO-trifluoroethyl amide enhances autophagic clearance and viability of \u03b2-cells in a setting of oxidative stress","volume":"588","author":"Li","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"46763","DOI":"10.1038\/srep46763","article-title":"Fucoxanthin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE and Nrf2-autophagy pathways","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.redox.2018.09.004","article-title":"Transient acceleration of autophagic degradation by pharmacological Nrf2 activation is important for retinal pigment epithelium cell survival","volume":"19","author":"Saito","year":"2018","journal-title":"Redox Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"24933","DOI":"10.1038\/srep24933","article-title":"Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors","volume":"6","author":"Kim","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"11023","DOI":"10.1038\/s41598-017-11262-5","article-title":"Transcription factors NRF2 and HSF1 have opposing functions in autophagy","volume":"7","author":"Dikovskaya","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1007\/s11357-014-9626-3","article-title":"p62\/SQSTM1 at the interface of aging, autophagy, and disease","volume":"36","author":"Bitto","year":"2014","journal-title":"Age"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"jcs222836","DOI":"10.1242\/jcs.222836","article-title":"p62\/SQSTM1\u2014steering the cell through health and disease","volume":"131","author":"Komatsu","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_161","first-page":"1399","article-title":"p62\/sequestosome 1 as a regulator of proteasome inhibitor-induced autophagy in human retinal pigment epithelial cells","volume":"16","author":"Viiri","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3389\/fonc.2018.00210","article-title":"Activation of p62\/SQSTM1-Keap1-nuclear factor erythroid 2-related factor 2 pathway in cancer","volume":"8","author":"Ichimura","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3389\/fnmol.2018.00310","article-title":"p62-Keap1-NRF2-ARE pathway: A contentious player for selective targeting of autophagy, oxidative stress and mitochondrial dysfunction in prion diseases","volume":"11","author":"Shah","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"13561","DOI":"10.1073\/pnas.1121572109","article-title":"Keap1 degradation by autophagy for the maintenance of redox homeostasis","volume":"109","author":"Taguchi","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.bbamcr.2014.03.016","article-title":"p62 provides dual cytoprotection against oxidative stress in the retinal pigment epithelium","volume":"1843","author":"Wang","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1038\/ncomms4496","article-title":"Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52","volume":"5","author":"Jo","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1080\/15548627.2016.1208889","article-title":"Transcription factor NFE2L2\/NRF2 is a regulator of macroautophagy genes","volume":"12","author":"Pajares","year":"2016","journal-title":"Autophagy"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1089\/rej.2011.1220","article-title":"5\u2019-Adenosine monophosphate-activated protein kinase-mammalian target of rapamycin axis as therapeutic target for age-related macular degeneration","volume":"14","author":"Hyttinen","year":"2011","journal-title":"Rejuv. Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"3467","DOI":"10.1242\/jcs.203216","article-title":"A PGAM5-KEAP1-Nrf2 complex is required for stress-induced mitochondrial retrograde trafficking","volume":"130","author":"Plafker","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.exer.2013.10.024","article-title":"Nrf2 signaling is impaired in the aging RPE given an oxidative insult","volume":"119","author":"Sachdeva","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2741\/4088","article-title":"Association between polymorphism of the NQO1, NOS3 and NFE2L2 genes and AMD","volume":"18","author":"Synowiec","year":"2013","journal-title":"Front. Biosci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1158\/0008-5472.CAN-12-3386","article-title":"RXR\u03b1 inhibits the NRF2-ARE signaling pathway through a direct interaction with the Neh7 domain of NRF2","volume":"73","author":"Wang","year":"2013","journal-title":"Cancer Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"19589","DOI":"10.1073\/pnas.0709483104","article-title":"Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha","volume":"104","author":"Wang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.neuro.2018.09.005","article-title":"Inhibition of NRF2 signaling and increased reactive oxygen species during embryogenesis in a rat model of retinoic acid-induced neural tube defects","volume":"69","author":"Liu","year":"2018","journal-title":"Neurotoxicology"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1186\/s12967-016-1101-8","article-title":"Repressed SIRT1\/PGC-1\u03b1 pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration","volume":"14","author":"Golestaneh","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Maugeri, A., Barchitta, M., Mazzone, M.G., Giuliano, F., Basile, G., and Agodi, A. (2018). Resveratrol modulates SIRT1 and DNMT functions and restores LINE-1 methylation levels in ARPE-19 cells under oxidative stress and inflammation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072118"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"4628","DOI":"10.1167\/iovs.13-13732","article-title":"Fullerenol protects retinal pigment epithelial cells from oxidative stress-induced premature senescence via activating SIRT1","volume":"55","author":"Zhuge","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Kaarniranta, K., Kajdanek, J., Morawiec, J., Pawlowska, E., and B\u0142asiak, J. (2018). PGC-1\u03b1 protects RPE cells of the aging retina against oxidative stress-induced degeneration through the regulation of senescence and mitochondrial quality control. The significance for AMD pathogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082317"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1089\/ars.2012.4615","article-title":"p53 orchestrates the PGC-1\u03b1-mediated antioxidant response upon mild redox and metabolic imbalance","volume":"18","author":"Aquilano","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1074\/jbc.M113.512483","article-title":"Peroxisome proliferator-activated receptor \u03b3 co-activator 1-\u03b1 as a critical co-activator of the murine hepatic oxidative stress response and mitochondrial biogenesis in Staphylococcus aureus sepsis","volume":"289","author":"Cherry","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2006.09.024","article-title":"Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators","volume":"127","author":"Drori","year":"2006","journal-title":"Cell"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"dmm032698","DOI":"10.1242\/dmm.032698","article-title":"Pgc-1\u03b1 repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice","volume":"11","author":"Zhang","year":"2018","journal-title":"Dis. Model Mech."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.redox.2017.05.015","article-title":"Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration","volume":"13","author":"Ferrington","year":"2017","journal-title":"Redox Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1038\/jid.2011.56","article-title":"Heme oxygenase-1 protects human melanocytes from H2O2-induced oxidative stress via the Nrf2-ARE pathway","volume":"131","author":"Jian","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1755-148X.2007.00424.x","article-title":"The significance of Nrf2 pathway in (photo)-oxidative stress response in melanocytes and keratinocytes of the human epidermis","volume":"21","author":"Marrot","year":"2008","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Shin, J.M., Kim, M.Y., Sohn, K.C., Jung, S.Y., Lee, H.E., Lim, J.W., Kim, S., Lee, Y.H., Im, M., and Seo, Y.J. (2014). Nrf2 negatively regulates melanogenesis by modulating PI3K\/Akt signaling. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096035"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1089\/ars.2009.2737","article-title":"Epithelial-mesenchymal transition: From molecular mechanisms, redox regulation to implications in human health and disease","volume":"12","author":"Cannito","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1089\/ars.2011.4280","article-title":"EMT and oxidative stress: A bidirectional interplay affecting tumor malignancy","volume":"16","author":"Giannoni","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"17036","DOI":"10.1038\/sigtrans.2017.36","article-title":"Redox regulation in tumor cell epithelial-mesenchymal transition: Molecular basis and therapeutic strategy","volume":"2","author":"Jiang","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1152\/physrev.00021.2018","article-title":"Endothelial to mesenchymal transition: Role in physiology and in the pathogenesis of human diseases","volume":"99","author":"Jimenez","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1172\/JCI39104","article-title":"The basics of epithelial-mesenchymal transition","volume":"119","author":"Kalluri","year":"2009","journal-title":"Clin. Investig."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Cubillo, E., Diaz-Lopez, A., Cuevas, E.P., Moreno-Bueno, G., Peinado, H., Montes, A., Santos, V., Portillo, F., and Cano, A. (2013). E47 and Id1 interplay in epithelial-mesenchymal transition. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059948"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial-mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/cas.12630","article-title":"Epithelial-mesenchymal transition is regulated at post-transcriptional levels by transforming growth factor-\u03b2 signaling during tumor progression","volume":"106","author":"Saitoh","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/jcb.21695","article-title":"NF-kappaB and epithelial to mesenchymal transition of cancer","volume":"104","author":"Min","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1158\/0008-5472.CAN-11-4038","article-title":"Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2","volume":"72","author":"Cieply","year":"2012","journal-title":"Cancer Res."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1177\/1947601912458582","article-title":"Diverse roles for the paxillin family of proteins in cancer","volume":"3","author":"Deakin","year":"2012","journal-title":"Genes Cancer"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1177\/0022034512467352","article-title":"Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma","volume":"92","author":"Scanlon","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/35000034","article-title":"The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells","volume":"2","author":"Batlle","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1667\/RR0695.1","article-title":"Isoform-specific activation of latent transforming growth factor \u03b2 (LTGF-\u03b2) by reactive oxygen species","volume":"166","author":"Jobling","year":"2006","journal-title":"Radiat. Res."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"re8","DOI":"10.1126\/scisignal.2005189","article-title":"Signaling mechanism of the epithelial-mesenchymal transition","volume":"7","author":"Gonzalez","year":"2014","journal-title":"Sci. Signal."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"5154","DOI":"10.1074\/jbc.M411575200","article-title":"Novel function of androgen receptor-associated protein 55\/Hic-5 as a negative regulator of Smad3 signaling","volume":"280","author":"Wang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.3389\/fimmu.2018.01985","article-title":"A potential link between oxidative stress and endothelial-to-mesenchymal transition in systemic sclerosis","volume":"9","author":"Thuan","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2009.09.026","article-title":"Oxidative stress and glutathione in TGF-\u03b2-mediated fibrogenesis","volume":"48","author":"Liu","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.cellsig.2014.02.017","article-title":"Redox control of p53 in the transcriptional regulation of TGF-\u03b21 target genes through SMAD cooperativity","volume":"26","author":"Overstreet","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1165\/rcmb.2013-0519OC","article-title":"Mitochondrial-targeted antioxidant therapy decreases transforming growth factor-\u03b2-mediated collagen production in a murine asthma model","volume":"52","author":"Jaffer","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1080\/10715762.2018.1500020","article-title":"TGF-\u03b21 induces epithelial-to-mesenchymal transition via inhibiting mitochondrial functions in A549 cells","volume":"52","author":"Zhang","year":"2018","journal-title":"Free Radic. Res."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"De Paepe, B., and Van Coster, R. (2017). A critical assessment of the therapeutic potential of resveratrol supplements for treating mitochondrial disorders. Nutrients, 9.","DOI":"10.3390\/nu9091017"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12943-016-0577-4","article-title":"Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation","volume":"16","author":"Lee","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"357","DOI":"10.4161\/cam.25651","article-title":"Par6 is phosphorylated by aPKC to facilitate EMT","volume":"7","author":"Gunaratne","year":"2013","journal-title":"Cell Adhes. Migr."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/jcmm.13060","article-title":"Signalling pathways involved in hypoxia-induced renal fibrosis","volume":"21","author":"Liu","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/jcb.25074","article-title":"Regulation of hypoxia-inducible factor-1a by reactive oxygen species: New developments in an old debate","volume":"116","author":"Movafagh","year":"2015","journal-title":"J. Cell. Biochem."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"6299","DOI":"10.21873\/anticanres.12986","article-title":"Hypoxia stimulates the epithelial-to-mesenchymal transition in lung cancer cells through accumulation of nuclear \u03b2-catenin","volume":"38","author":"Liu","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"De Francesco, E.M., Maggiolini, M., and Musti, A.M. (2018). Crosstalk between Notch, HIF-1\u03b1 and GPER in breast cancer EMT. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072011"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"6392","DOI":"10.1073\/pnas.0802047105","article-title":"Notch signaling mediates hypoxia-induced tumor cell migration and invasion","volume":"105","author":"Sahlgren","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.arr.2009.06.002","article-title":"Regulatory role of HIF-1\u03b1 in the pathogenesis of age-related macular degeneration (AMD)","volume":"8","author":"Arjamaa","year":"2009","journal-title":"Ageing Res. Rev."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.3892\/or.2014.3022","article-title":"Effects of the HIF-1\u03b1 and NF-\u03baB loop on epithelial-mesenchymal transition and chemoresistance induced by hypoxia in pancreatic cancer cells","volume":"31","author":"Cheng","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1093\/carcin\/bgn216","article-title":"Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells","volume":"29","author":"Cannito","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ceb.2017.10.008","article-title":"Multiprotein complexes governing Wnt signal transduction","volume":"51","author":"Gammons","year":"2018","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.3892\/or.2015.4504","article-title":"Resveratrol inhibits hypoxia-driven ROS-induced invasive and migratory ability of pancreatic cancer cells via suppression of the Hedgehog signaling pathway","volume":"35","author":"Li","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"5372","DOI":"10.1038\/onc.2014.466","article-title":"Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor","volume":"34","author":"Cui","year":"2015","journal-title":"Oncogene"},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Abba, M.L., Patil, N., Leupold, J.H., and Allgayer, H. (2016). MicroRNA regulation of epithelial to mesenchymal transition. J. Clin. Med., 5.","DOI":"10.3390\/jcm5010008"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ejphar.2016.12.003","article-title":"MicroRNAs-mediated epithelial-mesenchymal transition in fibrotic diseases","volume":"796","author":"Zou","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"38646","DOI":"10.1038\/srep38646","article-title":"Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis","volume":"16","author":"Zhou","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1159\/000494547","article-title":"Activation of Nrf2 by sulforaphane inhibits high glucose-induced progression of pancreatic cancer via AMPK dependent signaling","volume":"50","author":"Chen","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.bbrc.2017.06.074","article-title":"Rapamycin protects against paraquat-induced pulmonary fibrosis: Activation of Nrf2 signaling pathway","volume":"490","author":"Xu","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_227","first-page":"8862","article-title":"Downregulation of HMGB1 is required for the protective role of Nrf2 in EMT-mediated PF","volume":"2018","author":"Qu","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.molcel.2009.07.025","article-title":"KEAP1 E3 ligase-mediated downregulation of NF-kappaB signaling by targeting IKK\u03b2","volume":"3","author":"Lee","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1136\/annrheumdis-2014-206214","article-title":"Activating transcription factor 3 regulates canonical TGF\u03b2 signalling in systemic sclerosis","volume":"75","author":"Mallano","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Ryoo, I.G., Ha, H., and Kwak, M.K. (2014). Inhibitory role of the KEAP1-NRF2 pathway in TGF\u03b21-stimulated renal epithelial transition to fibroblastic cells: A modulatory effect on SMAD signaling. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093265"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/nar\/gkp865","article-title":"Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes","volume":"38","author":"Kim","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"14841","DOI":"10.1074\/jbc.M513737200","article-title":"Glycogen synthase kinase-3\u03b2 inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor Nrf2","volume":"281","author":"Salazar","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1007\/s00018-012-1170-7","article-title":"A Smurf1 tale: Function and regulation of an ubiquitin ligase in multiple cellular networks","volume":"70","author":"Cao","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.freeradbiomed.2017.12.013","article-title":"CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys","volume":"115","author":"Gong","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ejphar.2019.01.015","article-title":"CKIP-1 alleviates oxygen-glucose deprivation\/reoxygenation-induced apoptosis and oxidative stress in cultured hippocampal neurons by downregulating Keap1 and activating Nrf2\/ARE signaling","volume":"848","author":"Xiang","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1111\/jcmm.14241","article-title":"Nrf2 promotes breast cancer cell migration via up-regulation of G6PD\/HIF-1\u03b1\/Notch1 axis","volume":"23","author":"Zhang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"e1696","DOI":"10.1038\/cddis.2015.36","article-title":"Autophagy is a regulator of TGF-\u03b21-induced fibrogenesis in primary human atrial myofibroblasts","volume":"6","author":"Ghavami","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cyto.2014.07.249","article-title":"The effect of transforming growth factor \u03b21 on the crosstalk between autophagy and apoptosis in the annulus fibrosus cells under serum deprivation","volume":"70","author":"Ni","year":"2014","journal-title":"Cytokine"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"13122","DOI":"10.18632\/oncotarget.7536","article-title":"AEG-1\/MTDH-activated autophagy enhances human malignant glioma susceptibility to TGF-\u03b21-triggered epithelial-mesenchymal transition","volume":"7","author":"Zou","year":"2016","journal-title":"Oncotarget"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"364","DOI":"10.4161\/15384101.2014.987619","article-title":"SQSTM1\/p62 regulates the expression of junctional proteins through epithelial-mesenchymal transition factors","volume":"14","author":"Bertrand","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_241","first-page":"3607","article-title":"Autophagy regulates TGF-\u03b22-induced epithelial-mesenchymal transition in human retinal pigment epithelium cells","volume":"17","author":"Wu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1128\/MCB.00166-09","article-title":"Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains","volume":"29","author":"Bellot","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"6229","DOI":"10.1128\/MCB.02246-06","article-title":"BNIP3 is an RB\/E2F target gene required for hypoxia-induced autophagy","volume":"27","author":"Tracy","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"e1880","DOI":"10.1038\/cddis.2015.249","article-title":"Autophagy regulates hepatocyte identity and epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions promoting Snail degradation","volume":"6","author":"Grassi","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"507","DOI":"10.7150\/ijbs.30575","article-title":"Autophagy resists EMT process to maintain retinal pigment epithelium homeostasis","volume":"15","author":"Feng","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ophtha.2013.10.019","article-title":"Risk of scar in the comparison of age-related macular degeneration treatments trials","volume":"121","author":"Daniel","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_247","first-page":"747","article-title":"Choroidal neovascularization: A wound healing perspective","volume":"9","author":"Kent","year":"2003","journal-title":"Mol. Vis."},{"key":"ref_248","doi-asserted-by":"crossref","unstructured":"Priglinger, C.S., Obermann, J., Szober, C.M., Merl-Pham, J., Ohmayer, U., Behler, J., Gruhn, F., Kreutzer, T.C., Wertheimer, C., and Geerlof, A. (2016). Epithelial-to-mesenchymal transition of RPE cells in vitro confers increased \u03b21,6-N-glycosylation and increased susceptibility to galectin-3 binding. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146887"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1096\/fj.201801227R","article-title":"Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition","volume":"33","author":"Wu","year":"2019","journal-title":"FASEB J."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"e201800212","DOI":"10.26508\/lsa.201800212","article-title":"Loss of PGC-1\u03b1 in RPE induces mesenchymal transition and promotes retinal degeneration","volume":"2","author":"Rosales","year":"2019","journal-title":"Life Sci. Alliance"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"AMD104","DOI":"10.1167\/iovs.18-24132","article-title":"A role for \u03b2A3\/A1-crystallin in type 2 EMT of RPE cells occurring in dry age-related macular degeneration","volume":"9","author":"Ghosh","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"480","DOI":"10.4161\/auto.27292","article-title":"Lysosomal-mediated waste clearance in retinal pigment epithelial cells is regulated by CRYBA1\/\u03b2A3\/A1-crystallin via V-ATPase-MTORC1 signaling","volume":"10","author":"Valapala","year":"2014","journal-title":"Autophagy"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.ajpath.2015.11.014","article-title":"\u03b1B-crystallin regulates subretinal fibrosis by modulation of epithelial-mesenchymal transition","volume":"186","author":"Ishikawa","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"10892","DOI":"10.1074\/jbc.M800102200","article-title":"Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/onc.2008.392","article-title":"Hypoxia-activated autophagy accelerates degradation of SQSTM1\/p62","volume":"28","author":"Pursiheimo","year":"2009","journal-title":"Oncogene"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/15548627.2016.1256932","article-title":"Autophagy and KRT8\/keratin 8 protect degeneration of retinal pigment epithelium under oxidative stress","volume":"13","author":"Baek","year":"2017","journal-title":"Autophagy"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1167\/iovs.18-25678","article-title":"Suppression of epithelial-mesenchymal transition in retinal pigment epithelial cells by an MRTF-A inhibitor","volume":"60","author":"Kobayashi","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00109-015-1289-8","article-title":"Attenuation of EMT in RPE cells and subretinal fibrosis by an RAR-\u03b3 agonist","volume":"93","author":"Kimura","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.fct.2018.09.023","article-title":"The cigarette smoke components induced the cell proliferation and epithelial to mesenchymal transition via production of reactive oxygen species in endometrial adenocarcinoma cells","volume":"121","author":"Kim","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.biocel.2018.08.006","article-title":"Blue light emitting diodes irradiation causes cell death in colorectal cancer by inducing ROS production and DNA damage","volume":"103","author":"Yan","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"7304","DOI":"10.1523\/JNEUROSCI.0190-15.2015","article-title":"Investigating mitochondria as a target for treating age-related macular degeneration","volume":"35","author":"Terluk","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1007\/s00018-018-2843-7","article-title":"Mitochondrial quality control in AMD: Does mitophagy play a pivotal role?","volume":"75","author":"Hyttinen","year":"2018","journal-title":"Mol. Cell. Life Sci."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"424","DOI":"10.4103\/jovr.jovr_182_17","article-title":"The role of mitochondria in AMD: Current knowledge and future applications","volume":"12","author":"Kuppermann","year":"2017","journal-title":"J. Ophthalmic Vis. Res."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1038\/onc.2010.146","article-title":"Mitochondrial pyrimidine nucleotide carrier (PNC1) regulates mitochondrial biogenesis and the invasive phenotype of cancer cells","volume":"29","author":"Favre","year":"2010","journal-title":"Oncogene"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1007\/s00018-015-2122-9","article-title":"TUFM downregulation induces epithelial-mesenchymal transition and invasion in lung cancer cells via a mechanism involving AMPK-GSK3\u03b2 signaling","volume":"73","author":"He","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"4901","DOI":"10.18632\/oncotarget.13612","article-title":"Depletion of mitochondrial reactive oxygen species downregulates epithelial-to-mesenchymal transition in cervical cancer cells","volume":"8","author":"Shagieva","year":"2017","journal-title":"Oncotarget"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00441-016-2464-0","article-title":"Epithelial-mesenchymal transition in tissue repair and fibrosis","volume":"365","author":"Stone","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.exer.2017.08.001","article-title":"An inducible form of Nrf2 confers enhanced protection against acute oxidative stresses in RPE cells","volume":"164","author":"Vu","year":"2017","journal-title":"Exp. Eye Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/22\/5800\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:35:29Z","timestamp":1760189729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/22\/5800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,18]]},"references-count":268,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["ijms20225800"],"URL":"https:\/\/doi.org\/10.3390\/ijms20225800","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,18]]}}}