{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:27Z","timestamp":1787022087144,"version":"build-2736575974"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"national eye institute of the national institutes of health","award":["NEI P30EY029220"],"award-info":[{"award-number":["NEI P30EY029220"]}]},{"name":"mary d. allen foundation"},{"name":"dorie miller"},{"DOI":"10.13039\/100001818","name":"research to prevent blindness","doi-asserted-by":"publisher","award":["Unrestricted Grant to the Department of Ophthalmology, NY 10022"],"award-info":[{"award-number":["Unrestricted Grant to the Department of Ophthalmology, NY 10022"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Matrix metalloproteinases (MMPs) are involved in the pathology of numerous inflammatory retinal degenerations, including retinitis pigmentosa (RP). Our previous work revealed that intravitreal injections with tissue inhibitor of metalloproteinases 1 (TIMP-1) reduce the progression of rod cell death and inhibit cone cell remodeling that involves reactive gliosis in retinal M\u00fcller glial cells (MGCs) in rodent models. The underlying cellular and molecular mechanisms of how TIMP-1 functions in the retina remain to be resolved; however, MGCs are involved in structural homeostasis, neuronal cell survival and death. In the present study, MMP-9 and TIMP-1 expression patterns were investigated in a human MGC line (MIO-M1) under inflammatory cytokine (IL-1\u03b2 and TNF-\u03b1) and oxidative stress (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) conditions. First, both IL-1\u03b2 and TNF-\u03b1, but not H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2,<\/jats:sub>\n                    have a mild\n                    <jats:italic>in vitro<\/jats:italic>\n                    pro-survival effect on MIO-M1 cells. Treatment with either cytokine results in the imbalanced secretion of MMP-9 and TIMP-1. H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    treatment has little effect on their secretion. The investigation of their intracellular expression led to interesting observations. MMP-9 and TIMP-1 are both expressed, not only in the cytoplasm, but also inside the nucleus. None of the treatments alters the MMP-9 intracellular distribution pattern. In contrast to MMP-9, TIMP-1 is detected as speckles. Intracellular TIMP-1 aggregation forms in the cytoplasmic area with IL-1\u03b2 treatment. With H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    treatments, the cell morphology changes from cobbles to spindle shapes and the nuclei become larger with increases in TIMP-1 speckles in an H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    dose-dependent manner. Two TIMP-1 cell surface receptors, low density lipoprotein receptor-related protein-1 (LRP-1) and cluster of differentiation 82 (CD82), are expressed within the nucleus of MIO-M1 cells. Overall, these observations suggest that intracellular TIMP-1 is a target of proinflammatory and oxidative insults in the MGCs. Given the importance of the roles for MGCs in the retina, the functional implication of nuclear TIMP-1 and MMP-9 in MGCs is discussed.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0253915","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T13:32:10Z","timestamp":1626442330000},"page":"e0253915","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) are localized in the nucleus of retinal M\u00fcller glial cells and modulated by cytokines and oxidative stress"],"prefix":"10.1371","volume":"16","author":[{"given":"Eun-Jin","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-5807","authenticated-orcid":true,"given":"Mengmei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl Mae","family":"Craft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-813X","authenticated-orcid":true,"given":"Shinwu","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"issue":"2","key":"pone.0253915.ref001","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.exer.2005.03.006","article-title":"Retinal remodeling during retinal degeneration","volume":"81","author":"BW Jones","year":"2005","journal-title":"Experimental eye research"},{"issue":"2","key":"pone.0253915.ref002","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1385\/MN:28:2:139","article-title":"Retinal remodeling in inherited photoreceptor degenerations","volume":"28","author":"RE Marc","year":"2003","journal-title":"Molecular neurobiology"},{"issue":"1","key":"pone.0253915.ref003","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1080\/15384101.2018.1558873","article-title":"Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis","volume":"18","author":"L Donato","year":"2019","journal-title":"Cell Cycle"},{"issue":"1","key":"pone.0253915.ref004","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ophtha.2012.07.006","article-title":"Clinical evidence of sustained chronic inflammatory reaction in retinitis pigmentosa","volume":"120","author":"N Yoshida","year":"2013","journal-title":"Ophthalmology"},{"issue":"4","key":"pone.0253915.ref005","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.preteyeres.2006.05.003","article-title":"Muller cells in the healthy and diseased retina","volume":"25","author":"A Bringmann","year":"2006","journal-title":"Progress in retinal and eye research"},{"key":"pone.0253915.ref006","doi-asserted-by":"crossref","first-page":"2954721","DOI":"10.1155\/2016\/2954721","article-title":"Retinal Macroglial Responses in Health and Disease","volume":"2016","author":"R de Hoz","year":"2016","journal-title":"Biomed Res Int"},{"issue":"3","key":"pone.0253915.ref007","doi-asserted-by":"crossref","first-page":"e0120415","DOI":"10.1371\/journal.pone.0120415","article-title":"Muller glia activation in response to inherited retinal degeneration is highly varied and disease-specific","volume":"10","author":"C Hippert","year":"2015","journal-title":"PloS one"},{"issue":"6","key":"pone.0253915.ref008","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.preteyeres.2009.07.001","article-title":"Cellular signaling and factors involved in Muller cell gliosis: neuroprotective and detrimental effects.","volume":"28","author":"A Bringmann","year":"2009","journal-title":"Progress in retinal and eye research"},{"issue":"5","key":"pone.0253915.ref009","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/S0002-9440(10)61131-5","article-title":"Differential expression of matrix metalloproteinases 2 and 9 by glial Muller cells: response to soluble and extracellular matrix-bound tumor necrosis factor-alpha","volume":"160","author":"GA Limb","year":"2002","journal-title":"The American journal of pathology"},{"issue":"1","key":"pone.0253915.ref010","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1167\/iovs.04-0860","article-title":"Expression of acute-phase response proteins in retinal Muller cells in diabetes","volume":"46","author":"C Gerhardinger","year":"2005","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"pone.0253915.ref011","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00018-013-1457-3","article-title":"Cytokine functions of TIMP-1. 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Vargas","year":"2017","journal-title":"PloS one"},{"issue":"1","key":"pone.0253915.ref018","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1167\/iovs.14-15398","article-title":"The effect of TIMP-1 on the cone mosaic in the retina of the rat model of retinitis pigmentosa","volume":"56","author":"Y Ji","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"pone.0253915.ref019","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.exer.2015.08.005","article-title":"TIMP-1 affects the spatial distribution of dendritic processes of second-order neurons in a rat model of Retinitis Pigmentosa","volume":"140","author":"JA Shin","year":"2015","journal-title":"Experimental eye research"},{"issue":"1","key":"pone.0253915.ref020","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.tcb.2018.08.006","article-title":"Recognizing the Molecular Multifunctionality and Interactome of TIMP-1","volume":"29","author":"B Grunwald","year":"2019","journal-title":"Trends Cell Biol"},{"issue":"2","key":"pone.0253915.ref021","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1006\/bbrc.1999.0408","article-title":"binds to the cell surface and translocates to the nucleus of human MCF-7 breast carcinoma cells","volume":"257","author":"LM Ritter","year":"1999","journal-title":"Biochemical and biophysical research communications"},{"issue":"Pt 9","key":"pone.0253915.ref022","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1242\/jcs.111.9.1147","article-title":"Cell cycle-associated accumulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) in the nuclei of human gingival fibroblasts","volume":"111","author":"WQ Zhao","year":"1998","journal-title":"Journal of cell science"},{"issue":"3","key":"pone.0253915.ref023","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"V Vichai","year":"2006","journal-title":"Nat Protoc"},{"issue":"5","key":"pone.0253915.ref024","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1016\/j.ajpath.2012.01.025","article-title":"Interaction of clusterin and matrix metalloproteinase-9 and its implication for epithelial homeostasis and inflammation","volume":"180","author":"S Jeong","year":"2012","journal-title":"The American journal of pathology"},{"issue":"1\u20132","key":"pone.0253915.ref025","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"T Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"issue":"11","key":"pone.0253915.ref026","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1016\/j.bbamcr.2017.05.013","article-title":"New intracellular activities of matrix metalloproteinases shine in the moonlight","volume":"1864","author":"PG Jobin","year":"2017","journal-title":"Biochimica et biophysica acta Molecular cell research"},{"issue":"3","key":"pone.0253915.ref027","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1074\/jbc.R111.304428","article-title":"Loss of daylight vision in retinal degeneration: are oxidative stress and metabolic dysregulation to blame?","volume":"287","author":"C Punzo","year":"2012","journal-title":"The Journal of biological chemistry"},{"issue":"2","key":"pone.0253915.ref028","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jvs.2015.10.065","article-title":"Clearance of matrix metalloproteinase-9 is dependent on low-density lipoprotein receptor-related protein-1 expression downregulated by microRNA-205 in human abdominal aortic aneurysm","volume":"65","author":"CY Chan","year":"2017","journal-title":"Journal of vascular surgery"},{"issue":"7","key":"pone.0253915.ref029","doi-asserted-by":"crossref","first-page":"e103839","DOI":"10.1371\/journal.pone.0103839","article-title":"Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities.","volume":"9","author":"J Thevenard","year":"2014","journal-title":"PloS one"},{"issue":"17","key":"pone.0253915.ref030","doi-asserted-by":"crossref","first-page":"3934","DOI":"10.1038\/sj.emboj.7601281","article-title":"Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein","volume":"25","author":"KK Jung","year":"2006","journal-title":"The EMBO journal"},{"issue":"4","key":"pone.0253915.ref031","doi-asserted-by":"crossref","first-page":"6496","DOI":"10.18632\/oncotarget.14133","article-title":"TIMP-1 and CD82, a promising combined evaluation marker for PDAC","volume":"8","author":"J Zhang","year":"2017","journal-title":"Oncotarget"},{"issue":"2","key":"pone.0253915.ref032","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","article-title":"The role of oxidative stress in the pathogenesis of age-related macular degeneration","volume":"45","author":"S Beatty","year":"2000","journal-title":"Survey of ophthalmology"},{"issue":"2","key":"pone.0253915.ref033","first-page":"137","article-title":"Breast cancer; tumor neovasculature and the effect of tissue inhibitor of metalloproteinases-1 (TIMP-1) on angiogenesis","volume":"10","author":"UP Thorgeirsson","year":"1996","journal-title":"In Vivo"},{"issue":"7","key":"pone.0253915.ref034","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1007\/s10495-010-0498-4","article-title":"IL-1beta induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells","volume":"15","author":"G Verma","year":"2010","journal-title":"Apoptosis"},{"issue":"27","key":"pone.0253915.ref035","doi-asserted-by":"crossref","first-page":"re6","DOI":"10.1126\/scisignal.127re6","article-title":"Tissue inhibitors of metalloproteinases in cell signaling: metalloproteinase-independent biological activities","volume":"1","author":"WG Stetler-Stevenson","year":"2008","journal-title":"Science signaling"},{"issue":"1","key":"pone.0253915.ref036","first-page":"196","article-title":"Microglial cells invade the outer retina as photoreceptors degenerate in Royal College of Surgeons rats","volume":"37","author":"RS Roque","year":"1996","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"pone.0253915.ref037","doi-asserted-by":"crossref","first-page":"e0177224","DOI":"10.1371\/journal.pone.0177224","article-title":"Strong upregulation of inflammatory genes accompanies photoreceptor demise in canine models of retinal degeneration","volume":"12","author":"T Appelbaum","year":"2017","journal-title":"PloS one"},{"issue":"1","key":"pone.0253915.ref038","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1016\/j.ophtha.2012.07.008","article-title":"Laboratory evidence of sustained chronic inflammatory reaction in retinitis pigmentosa","volume":"120","author":"N Yoshida","year":"2013","journal-title":"Ophthalmology"},{"key":"pone.0253915.ref039","first-page":"616","article-title":"Retinal neuronal MCP-1 induced by AGEs stimulates TNF-alpha expression in rat microglia via p38, ERK, and","volume":"20","author":"N Dong","year":"2014","journal-title":"NF-kappaB pathways. Molecular vision"},{"issue":"15","key":"pone.0253915.ref040","first-page":"6524","article-title":"Tumor necrosis factor-alpha is produced by dying retinal neurons and is required for Muller glia proliferation during zebrafish retinal regeneration. The Journal of neuroscience: the official journal of the","volume":"33","author":"CM Nelson","year":"2013","journal-title":"Society for Neuroscience"},{"issue":"3","key":"pone.0253915.ref041","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.cardiores.2005.12.002","article-title":"Structure and function of matrix metalloproteinases and TIMPs","volume":"69","author":"H Nagase","year":"2006","journal-title":"Cardiovasc Res"},{"key":"pone.0253915.ref042","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/1471-2407-9-188","article-title":"Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature","volume":"9","author":"A Kohrmann","year":"2009","journal-title":"BMC cancer"},{"key":"pone.0253915.ref043","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.neuroscience.2012.06.019","article-title":"Intranuclear matrix metalloproteinases promote DNA damage and apoptosis induced by oxygen-glucose deprivation in neurons","volume":"220","author":"JW Hill","year":"2012","journal-title":"Neuroscience"},{"issue":"1","key":"pone.0253915.ref044","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1471-4159.2009.06433.x","article-title":"Increased intranuclear matrix metalloproteinase activity in neurons interferes with oxidative DNA repair in focal cerebral ischemia","volume":"112","author":"Y Yang","year":"2010","journal-title":"Journal of neurochemistry"},{"issue":"3","key":"pone.0253915.ref045","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/glia.20927","article-title":"Differential vesicular distribution and trafficking of MMP-2, MMP-9, and their inhibitors in astrocytes","volume":"58","author":"O Sbai","year":"2010","journal-title":"Glia"},{"issue":"2","key":"pone.0253915.ref046","first-page":"155","article-title":"Nuclear localization of catalytically active MMP-2 in endothelial cells and neurons","volume":"6","author":"SK Sinha","year":"2014","journal-title":"American journal of translational research"},{"issue":"4","key":"pone.0253915.ref047","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.2353\/ajpath.2006.060005","article-title":"Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis","volume":"169","author":"K Si-Tayeb","year":"2006","journal-title":"The American journal of pathology"},{"issue":"8","key":"pone.0253915.ref048","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/boc.201300020","article-title":"Nuclear MMP-9 role in the regulation of rat skeletal myoblasts proliferation","volume":"105","author":"M Zimowska","year":"2013","journal-title":"Biol Cell"},{"issue":"5","key":"pone.0253915.ref049","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nm.3508","article-title":"A new transcriptional role for matrix metalloproteinase-12 in antiviral immunity","volume":"20","author":"DJ Marchant","year":"2014","journal-title":"Nat Med"},{"issue":"2","key":"pone.0253915.ref050","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/jcbfm.2008.130","article-title":"Matrix metalloproteinase-13 is activated and is found in the nucleus of neural cells after cerebral ischemia. Journal of cerebral blood flow and metabolism: official journal of the","volume":"29","author":"E Cuadrado","year":"2009","journal-title":"International Society of Cerebral Blood Flow and Metabolism"},{"issue":"3","key":"pone.0253915.ref051","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/mc.20270","article-title":"Atypical localization of membrane type 1-matrix metalloproteinase in the nucleus is associated with aggressive features of hepatocellular carcinoma","volume":"46","author":"YC Ip","year":"2007","journal-title":"Mol Carcinog"},{"issue":"1","key":"pone.0253915.ref052","doi-asserted-by":"crossref","first-page":"e84748","DOI":"10.1371\/journal.pone.0084748","article-title":"Matrix metalloproteinase 3 promotes cellular anti-dengue virus response via interaction with transcription factor NFkappaB in cell nucleus","volume":"9","author":"X Zuo","year":"2014","journal-title":"PloS one"},{"issue":"30","key":"pone.0253915.ref053","doi-asserted-by":"crossref","first-page":"47609","DOI":"10.18632\/oncotarget.10251","article-title":"MMP7 interacts with ARF in nucleus to potentiate tumor microenvironments for prostate cancer progression in vivo","volume":"7","author":"Y Xie","year":"2016","journal-title":"Oncotarget"},{"key":"pone.0253915.ref054","doi-asserted-by":"crossref","first-page":"17036","DOI":"10.1038\/cddiscovery.2017.36","article-title":"Nuclear matrix metalloproteinases: functions resemble the evolution from the intracellular to the extracellular compartment","volume":"3","author":"Y Xie","year":"2017","journal-title":"Cell Death Discov"},{"issue":"18","key":"pone.0253915.ref055","doi-asserted-by":"crossref","first-page":"15498","DOI":"10.1074\/jbc.M100121200","article-title":"The low density lipoprotein receptor-related protein modulates levels of matrix metalloproteinase 9 (MMP-9) by mediating its cellular catabolism","volume":"276","author":"E Hahn-Dantona","year":"2001","journal-title":"The Journal of biological chemistry"},{"issue":"47","key":"pone.0253915.ref056","doi-asserted-by":"crossref","first-page":"ra15","DOI":"10.1126\/scisignal.1164263","article-title":"Gamma-secretase limits the inflammatory response through the processing of LRP1","volume":"1","author":"K Zurhove","year":"2008","journal-title":"Science signaling"},{"issue":"3\u20134","key":"pone.0253915.ref057","first-page":"133","article-title":"Cell cycle-dependent localization of tissue inhibitor of metalloproteinases-1 immunoreactivity in cultured human gingival fibroblasts","volume":"58","author":"H Li","year":"1995","journal-title":"Nagoya journal of medical science"},{"issue":"15","key":"pone.0253915.ref058","doi-asserted-by":"crossref","first-page":"8503","DOI":"10.1073\/pnas.1918944117","article-title":"Nonclassical nuclear localization signals mediate nuclear import of CIRBP","volume":"117","author":"B Bourgeois","year":"2020","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"2","key":"pone.0253915.ref059","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a000646","article-title":"Nuclear speckles","volume":"3","author":"DL Spector","year":"2011","journal-title":"Cold Spring Harbor perspectives in biology"},{"issue":"12","key":"pone.0253915.ref060","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1083\/jcb.201904098","article-title":"Stress granules regulate stress-induced paraspeckle assembly","volume":"218","author":"H An","year":"2019","journal-title":"The Journal of cell biology"},{"key":"pone.0253915.ref061","first-page":"283","article-title":"Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system","volume":"16","author":"L Bhatt","year":"2010","journal-title":"Molecular vision"},{"issue":"5","key":"pone.0253915.ref062","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1111\/j.1471-4159.2009.06081.x","article-title":"Stress-induced activation of Nox contributes to cell survival signalling via production of hydrogen peroxide","volume":"109","author":"G Groeger","year":"2009","journal-title":"Journal of neurochemistry"},{"issue":"8","key":"pone.0253915.ref063","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1038\/cdd.2008.43","article-title":"Redox survival signalling in retina-derived 661W cells","volume":"15","author":"AM Mackey","year":"2008","journal-title":"Cell Death Differ"},{"key":"pone.0253915.ref064","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.3389\/fphar.2018.01280","article-title":"Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as","volume":"9","author":"I Bellezza","year":"2018","journal-title":"Therapeutic Target. Frontiers in pharmacology"},{"issue":"5782","key":"pone.0253915.ref065","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1126\/science.1130481","article-title":"Cell signaling. H2O2, a necessary evil for cell signaling","volume":"312","author":"SG Rhee","year":"2006","journal-title":"Science"},{"key":"pone.0253915.ref066","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1038\/cddis.2011.96","article-title":"Hydrogen peroxide: a Jekyll and Hyde signalling molecule","volume":"2","author":"DR Gough","year":"2011","journal-title":"Cell death & disease"},{"key":"pone.0253915.ref067","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.freeradbiomed.2015.04.009","article-title":"Sigma 1 receptor regulates the oxidative stress response in primary retinal Muller glial cells via NRF2 signaling and system xc(-), the Na(+)-independent glutamate-cystine exchanger","volume":"86","author":"J Wang","year":"2015","journal-title":"Free radical biology & medicine"},{"key":"pone.0253915.ref068","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12915-015-0137-1","article-title":"Expression of leukemia inhibitory factor in Muller glia cells is regulated by a redox-dependent mRNA stability mechanism","volume":"13","author":"C Agca","year":"2015","journal-title":"BMC Biol"},{"issue":"1","key":"pone.0253915.ref069","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41598-018-36917-9","article-title":"TGF-beta-SNAIL axis induces Muller glial-mesenchymal transition in the pathogenesis of idiopathic epiretinal membrane","volume":"9","author":"A Kanda","year":"2019","journal-title":"Scientific reports"},{"issue":"3","key":"pone.0253915.ref070","first-page":"2339","article-title":"Reactive oxygen species induce epithelialmesenchymal transition, glycolytic switch, and mitochondrial repression through the Dlx2\/Snail signaling pathways in MCF7 cells","volume":"20","author":"SY Lee","year":"2019","journal-title":"Molecular medicine reports"},{"issue":"Pt 15","key":"pone.0253915.ref071","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1242\/jcs.00618","article-title":"DYRK1A accumulates in splicing speckles through a novel targeting signal and induces speckle disassembly","volume":"116","author":"M Alvarez","year":"2003","journal-title":"Journal of cell science"},{"issue":"6","key":"pone.0253915.ref072","doi-asserted-by":"crossref","first-page":"4065","DOI":"10.1128\/IAI.69.6.4065-4071.2001","article-title":"Trichinella spiralis-infected muscle cells: abundant RNA polymerase II in nuclear speckle domains colocalizes with nuclear antigens","volume":"69","author":"C Yao","year":"2001","journal-title":"Infect Immun"},{"key":"pone.0253915.ref073","first-page":"1197","article-title":"Gene expression changes within Muller glial cells in retinitis pigmentosa","volume":"18","author":"K Roesch","year":"2012","journal-title":"Molecular vision"},{"issue":"4","key":"pone.0253915.ref074","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1006\/jmbi.1998.2223","article-title":"Three-dimensional structure of human tissue inhibitor of metalloproteinases-2 at 2.1 A resolution","volume":"284","author":"A Tuuttila","year":"1998","journal-title":"Journal of molecular biology"},{"issue":"39","key":"pone.0253915.ref075","doi-asserted-by":"crossref","first-page":"11745","DOI":"10.1021\/bi00205a010","article-title":"Solution structure of the active domain of tissue inhibitor of metalloproteinases-2. A new member of the OB fold protein family","volume":"33","author":"RA Williamson","year":"1994","journal-title":"Biochemistry"},{"issue":"4","key":"pone.0253915.ref076","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3109\/10409238.2010.488216","article-title":"Oligonucleotide\/oligosaccharide-binding fold proteins: a growing family of genome guardians","volume":"45","author":"RL Flynn","year":"2010","journal-title":"Critical reviews in biochemistry and molecular biology"},{"key":"pone.0253915.ref077","doi-asserted-by":"crossref","first-page":"101084","DOI":"10.1016\/j.redox.2018.101084","article-title":"ROS and the DNA damage response in cancer","volume":"25","author":"US Srinivas","year":"2019","journal-title":"Redox Biol"},{"key":"pone.0253915.ref078","doi-asserted-by":"crossref","first-page":"2389523","DOI":"10.1155\/2018\/2389523","article-title":"Targeting Oxidatively Induced DNA Damage Response in Cancer: Opportunities for Novel Cancer Therapies.","volume":"2018","author":"P Davalli","year":"2018","journal-title":"Oxid Med Cell Longev"},{"issue":"1","key":"pone.0253915.ref079","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1038\/s41467-017-01805-9","article-title":"DNA damage causes rapid accumulation of phosphoinositides for ATR signaling","volume":"8","author":"YH Wang","year":"2017","journal-title":"Nat Commun"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253915","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T06:18:58Z","timestamp":1725430738000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0253915"}},"subtitle":[],"editor":[{"given":"Hemant","family":"Khanna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,16]]},"references-count":79,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0253915","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,16]]}}}