{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:36:26Z","timestamp":1781246186875,"version":"3.54.1"},"reference-count":88,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"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>Diabetic retinopathy (DR) is a common complication of diabetes that causes severe visual impairment globally. The pathogenesis of DR is related to oxidative stress and chronic inflammation. The fibroblast growth factor type 1 (FGF-1) mitogen plays crucial roles in cell function, development, and metabolism. FGF-1 is involved in blood sugar regulation and exerts beneficial antioxidative and anti-inflammatory effects on various organ systems. This study investigated the antioxidative and anti-inflammatory neuroprotective effects of FGF-1 on high-glucose-induced retinal damage. The results revealed that FGF-1 treatment significantly reversed the harmful effects of oxidative stress and inflammatory mediators in retinal tissue in a streptozotocin-induced diabetic rat model. These protective effects were also observed in the in vitro model of retinal ARPE-19 cells exposed to a high-glucose condition. We demonstrated that FGF-1 attenuated p38 mitogen-activated protein kinase and nuclear factor-\u03baB pathway activation under the high-glucose condition. Our results indicated that FGF-1 could effectively prevent retinal injury in diabetes. The findings of this study could be used to develop novel treatments for DR that aim to reduce the cascade of oxidative stress and inflammatory signals in neuroretinal tissue.<\/jats:p>","DOI":"10.3390\/ijms22137233","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T22:02:04Z","timestamp":1625522524000},"page":"7233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Fibroblast Growth Factor Type 1 Ameliorates High-Glucose-Induced Oxidative Stress and Neuroinflammation in Retinal Pigment Epithelial Cells and a Streptozotocin-Induced Diabetic Rat Model"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1066-2556","authenticated-orcid":false,"given":"Hsin-Wei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, No. 111, Sec. 3, Xinglong Rd., Taipei 11696, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, No. 1, Jen Ai Road Sec. 1, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-May","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Taiwan University Hospital, No. 7, Zhongshan South Road, Taipei 100, Taiwan"},{"name":"Department of Ophthalmology, College of Medicine, National Taiwan University, No. 1, Jen Ai Road, Sec. 1, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4328-8716","authenticated-orcid":false,"given":"Chang-Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Taiwan University Hospital, No. 7, Zhongshan South Road, Taipei 100, Taiwan"},{"name":"Department of Ophthalmology, College of Medicine, National Taiwan University, No. 1, Jen Ai Road, Sec. 1, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"945","DOI":"10.7326\/0003-4819-140-11-200406010-00035","article-title":"The Evolving Diabetes Burden in the United States","volume":"140","author":"Engelgau","year":"2004","journal-title":"Ann. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/09286580701396720","article-title":"Overview of Epidemiologic Studies of Diabetic Retinopathy","volume":"14","year":"2007","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11154-008-9090-4","article-title":"Oxidative stress and diabetic retinopathy: Pathophysiological mechanisms and treatment perspectives","volume":"9","author":"Kowluru","year":"2008","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"312","DOI":"10.4239\/wjd.v6.i2.312","article-title":"Current knowledge on diabetic retinopathy from human donor tissues","volume":"6","author":"Eisma","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s40135-019-00198-w","article-title":"Decision Making in Proliferative Diabetic Retinopathy Treatment","volume":"7","author":"Kansora","year":"2019","journal-title":"Curr. Ophthalmol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1900\/RDS.2015.12.196","article-title":"New Therapeutic Approaches in Diabetic Retinopathy","volume":"12","author":"Vaziri","year":"2015","journal-title":"Rev. Diabet. Stud."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1097\/ICU.0000000000000424","article-title":"Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: Recent clinically relevant findings from DRCR.net Protocol T","volume":"28","author":"Cai","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1159\/000459691","article-title":"Intravitreal Steroids in Diabetic Macular Edema","volume":"60","author":"Lattanzio","year":"2017","journal-title":"Dev. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1177\/2042018810396750","article-title":"Review of therapeutic advances in diabetic retinopathy","volume":"2","author":"Shah","year":"2011","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/IIO.0000000000000027","article-title":"Current management of vitreous hemorrhage due to proliferative diabetic retinopathy","volume":"54","author":"Carvounis","year":"2014","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/aos.12951","article-title":"Four-port bimanual 23-gauge vitrectomy for diabetic tractional retinal detachment","volume":"94","author":"Wang","year":"2016","journal-title":"Acta Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"412","DOI":"10.2337\/dc16-2641","article-title":"Diabetic Retinopathy: A Position Statement by the American Diabetes Association","volume":"40","author":"Solomon","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2337\/diacare.19.3.257","article-title":"Oxidative stress and diabetic vascular complications","volume":"19","author":"Giugliano","year":"1996","journal-title":"Diabetes Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/dmrr.196","article-title":"The role of oxidative stress in the onset and progression of diabetes and its complications: A summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society","volume":"17","author":"Nawroth","year":"2001","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.2174\/1381612043383124","article-title":"Advanced glycation and advanced lipoxidation: Possible role in initiation and progression of diabetic retinopathy","volume":"10","author":"Stitt","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.2174\/09298673113209990025","article-title":"Advanced glycation end products and diabetic retinopathy","volume":"20","author":"Chen","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.3389\/fendo.2020.621938","article-title":"The Role of Lipoxidation in the Pathogenesis of Diabetic Retinopathy","volume":"11","author":"Augustine","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fang, I.M., Yang, C.H., Yang, C.M., and Chen, M.S. (2013). Chitosan oligosaccharides attenuates oxidative-stress related retinal degeneration in rats. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077323"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yeh, P.-T., Huang, H.-W., Yang, C.-M., Yang, W.-S., and Yang, C.-H. (2016). Astaxanthin Inhibits Expression of Retinal Oxidative Stress and Inflammatory Mediators in Streptozotocin-Induced Diabetic Rats. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146438"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1167\/iovs.09-4575","article-title":"The role of TLR4 in photoreceptor {alpha}a crystallin upregulation during early experimental autoimmune uveitis","volume":"51","author":"Saraswathy","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.aanat.2019.01.006","article-title":"Localization of nitro-tyrosine immunoreactivity in human retina","volume":"223","author":"Nag","year":"2019","journal-title":"Ann. Anat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1167\/iovs.19-27346","article-title":"Unsaturated Aldehyde Acrolein Promotes Retinal Glial Cell Migration","volume":"60","author":"Murata","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0002-9440(10)63952-1","article-title":"Leukocyte-mediated endothelial cell injury and death in the diabetic retina","volume":"158","author":"Joussen","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1096\/fj.03-1476fje","article-title":"A central role for inflammation in the pathogenesis of diabetic retinopathy","volume":"18","author":"Joussen","year":"2004","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"R\u00fcbsam, A., Parikh, S., and Fort, P.E. (2018). Role of Inflammation in Diabetic Retinopathy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19040942"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/wdev.176","article-title":"The Fibroblast Growth Factor signaling pathway","volume":"4","author":"Ornitz","year":"2015","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1016\/S0021-9258(19)41631-1","article-title":"Purification of a fibroblast growth factor from bovine pituitary","volume":"250","author":"Gospodarowicz","year":"1975","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.1073\/pnas.86.19.7432","article-title":"Heparin-binding growth factor type 1 (acidic fibroblast growth factor): A potential biphasic autocrine and paracrine regulator of hepatocyte regeneration","volume":"86","author":"Kan","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1161\/01.RES.69.1.76","article-title":"Effects of acidic fibroblast growth factor on normal and ischemic myocardium","volume":"69","author":"Banai","year":"1991","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/MOH.0b013e3282f97d98","article-title":"Fibroblast growth factor regulation of neovascularization","volume":"15","author":"Murakami","year":"2008","journal-title":"Curr. Opin. Hematol."},{"key":"ref_31","first-page":"5365","article-title":"Experimental study of epidermal growth factor and acidic fibroblast growth factor in the treatment of diabetic foot wounds","volume":"15","author":"Xu","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_32","first-page":"II11","article-title":"Fibroblast growth factor-mediated angiogenesis for the treatment of ischemia. Lessons learned from experimental models and early human experience","volume":"17","author":"Goncalves","year":"1998","journal-title":"Rev. Port. Cardiol. Orgao Of. Soc. Port. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.jacc.2004.05.067","article-title":"Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: A fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism","volume":"44","author":"Palmen","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1093\/cvr\/cvx165","article-title":"A novel fibroblast growth factor-1 ligand with reduced heparin binding protects the heart against ischemia-reperfusion injury in the presence of heparin co-administration","volume":"113","author":"Huang","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3171\/SPI\/2008\/8\/3\/208","article-title":"Nerve repair using acidic fibroblast growth factor in human cervical spinal cord injury: A preliminary Phase I clinical study","volume":"8","author":"Wu","year":"2008","journal-title":"J. Neurosurg. Spine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature13540","article-title":"Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer","volume":"513","author":"Suh","year":"2014","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, C., Zhang, L., Chen, S., Feng, B., Lu, X., Bai, Y., Liang, G., Tan, Y., Shao, M., and Skibba, M. (2013). The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082287"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10557-016-6639-4","article-title":"Advanced Interfere Treatment of Diabetic Cardiomyopathy Rats by aFGF-Loaded Heparin-Modified Microbubbles and UTMD Technique","volume":"30","author":"Zhang","year":"2016","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1073\/pnas.1525093113","article-title":"Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease","volume":"113","author":"Liu","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.kint.2017.05.013","article-title":"Fibroblast growth factor 1 ameliorates diabetic nephropathy by an anti-inflammatory mechanism","volume":"93","author":"Liang","year":"2018","journal-title":"Kidney Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.diabres.2011.05.016","article-title":"Improved refractory wound healing with administration of acidic fibroblast growth factor in diabetic rats","volume":"93","author":"Xie","year":"2011","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0006-291X(90)91714-4","article-title":"Expression pattern of acidic and basic fibroblast growth factor genes in adult rat eyes","volume":"168","author":"Noji","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","first-page":"417","article-title":"Developmental regulation of acidic fibroblast growth factor (aFGF) expression in bovine retina","volume":"37","author":"Jacquemin","year":"1993","journal-title":"Int. J. Dev. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/jcb.240390204","article-title":"Immunological study of acidic fibroblast growth factor (aFGF) distribution in the eye","volume":"39","author":"Caruelle","year":"1989","journal-title":"J. Cell. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00441-009-0787-9","article-title":"Localization patterns of fibroblast growth factor 1 and its receptors FGFR1 and FGFR2 in postnatal mouse retina","volume":"336","author":"Catalani","year":"2009","journal-title":"Cell Tissue Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7042","DOI":"10.1073\/pnas.93.14.7042","article-title":"bcl-2 overexpression reduces apoptotic photoreceptor cell death in three different retinal degenerations","volume":"93","author":"Chen","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3109\/08977199809117186","article-title":"Paracrine effects of phosphorylated and excreted FGF1 by retinal pigmented epithelial cells","volume":"15","author":"Guillonneau","year":"1998","journal-title":"Growth Factors"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1038\/sj.onc.1203872","article-title":"Regulation of proliferation-survival decisions is controlled by FGF1 secretion in retinal pigmented epithelial cells","volume":"19","author":"Bryckaert","year":"2000","journal-title":"Oncogene"},{"key":"ref_49","first-page":"224","article-title":"Macular and peripheral distribution of ICAM-1 in the human choriocapillaris and retina","volume":"12","author":"Mullins","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1189\/jlb.0302117","article-title":"Role of MCP-1 and MIP-1alpha in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization","volume":"73","author":"Yoshida","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1073\/pnas.0608167104","article-title":"Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis","volume":"104","author":"Nakazawa","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13024-017-0175-y","article-title":"Microglia-derived IL-1\u03b2 promotes chemokine expression by M\u00fcller cells and RPE in focal retinal degeneration","volume":"12","author":"Natoli","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.3389\/fimmu.2019.01618","article-title":"IL-1 Family Members Mediate Cell Death, Inflammation and Angiogenesis in Retinal Degenerative Diseases","volume":"10","author":"Wooff","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.brainres.2007.01.097","article-title":"NMDA-induced interleukin-1beta expression is mediated by nuclear factor-kappa B p65 in the retina","volume":"1142","author":"Kitaoka","year":"2007","journal-title":"Brain Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/ceo.12696","article-title":"Diabetic retinopathy: Global prevalence, major risk factors, screening practices and public health challenges: A review","volume":"44","author":"Ting","year":"2016","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2174\/1570159X14666160614095559","article-title":"Neurodegeneration and Neuroinflammation in Diabetic Retinopathy: Potential Approaches to Delay Neuronal Loss","volume":"14","author":"Malaguarnera","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1167\/iovs.07-0764","article-title":"Beneficial effect of zeaxanthin on retinal metabolic abnormalities in diabetic rats","volume":"49","author":"Kowluru","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","first-page":"3801570","article-title":"Ocular Complications of Diabetes and Therapeutic Approaches","volume":"2016","author":"Karamichos","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3164734","DOI":"10.1155\/2016\/3164734","article-title":"The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults","volume":"2016","author":"Nita","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_60","first-page":"190724","article-title":"The retinal pigment epithelium: Something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy","volume":"2010","author":"Villarroel","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9702820","DOI":"10.1155\/2017\/9702820","article-title":"Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy","volume":"2017","author":"Li","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Willermain, F., Scifo, L., Weber, C., Caspers, L., Perret, J., and Delporte, C. (2018). Potential Interplay between Hyperosmolarity and Inflammation on Retinal Pigmented Epithelium in Pathogenesis of Diabetic Retinopathy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041056"},{"key":"ref_63","first-page":"8054073","article-title":"Improving the Reliability and Utility of Streptozotocin-Induced Rat Diabetic Model","volume":"2018","author":"Garyantes","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.niox.2008.09.001","article-title":"p38MAPK and ERK promote nitric oxide production in cultured human retinal pigmented epithelial cells induced by high concentration glucose","volume":"20","author":"Yuan","year":"2009","journal-title":"Nitric Oxide"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e206","DOI":"10.1111\/aos.13230","article-title":"Aqueous humour concentrations of TGF-\u03b2, PLGF and FGF-1 and total retinal blood flow in patients with early non-proliferative diabetic retinopathy","volume":"95","author":"Khuu","year":"2017","journal-title":"Acta Ophthalmol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"43603","DOI":"10.1155\/2007\/43603","article-title":"Oxidative stress and diabetic retinopathy","volume":"2007","author":"Kowluru","year":"2007","journal-title":"Exp. Diabetes Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8562408","DOI":"10.1155\/2019\/8562408","article-title":"Oxidative Stress as the Main Target in Diabetic Retinopathy Pathophysiology","volume":"2019","author":"Cecilia","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6294","DOI":"10.1111\/jcmm.13921","article-title":"Reduction of cellular stress is essential for Fibroblast growth factor 1 treatment for diabetic nephropathy","volume":"22","author":"Wu","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000478745","article-title":"Prevention of Diabetic Nephropathy by Modified Acidic Fibroblast Growth Factor","volume":"137","author":"Pena","year":"2017","journal-title":"Nephron"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1179\/135100003225002673","article-title":"The retina: Oxidative stress and diabetes","volume":"8","author":"Gillies","year":"2003","journal-title":"Redox Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications","volume":"107","author":"Giacco","year":"2010","journal-title":"Circ. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41419-019-1696-9","article-title":"FGF1\u0394HBS ameliorates chronic kidney disease via PI3K\/AKT mediated suppression of oxidative stress and inflammation","volume":"10","author":"Wang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.bbrc.2020.05.145","article-title":"Fibroblast growth factor 1 ameliorates diabetes-induced splenomegaly via suppressing inflammation and oxidative stress","volume":"528","author":"Wu","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1167\/iovs.04-1057","article-title":"Serum inflammatory markers in diabetic retinopathy","volume":"46","author":"Meleth","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_75","first-page":"44","article-title":"Serum inflammatory cytokines IL-1beta, IL-6, TNF-alpha and VEGF have influence on the development of diabetic retinopathy","volume":"53","author":"Sivkova","year":"2011","journal-title":"Folia Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8546423","DOI":"10.1155\/2018\/8546423","article-title":"Levels of Inflammatory Cytokines IL-1\u03b2, IL-6, IL-8, IL-17A, and TNF-\u03b1 in Aqueous Humour of Patients with Diabetic Retinopathy","volume":"2018","author":"Feng","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"962962","DOI":"10.1155\/2014\/962962","article-title":"A Network Map of FGF-1\/FGFR Signaling System","volume":"2014","author":"Raju","year":"2014","journal-title":"J. Signal Transduct."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"22367","DOI":"10.1074\/jbc.273.35.22367","article-title":"Endogenous FGF1-induced activation and synthesis of extracellular signal-regulated kinase 2 reduce cell apoptosis in retinal-pigmented epithelial cells","volume":"273","author":"Guillonneau","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1167\/iovs.14-15874","article-title":"Decorin Prevents Retinal Pigment Epithelial Barrier Breakdown under Diabetic Conditions by Suppressing p38 MAPK Activation","volume":"56","author":"Wang","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1172\/JCI3326","article-title":"Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways","volume":"103","author":"Igarashi","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1046\/j.1523-1755.2003.00836.x","article-title":"High glucose activates the p38 MAPK pathway in cultured human peritoneal mesothelial cells","volume":"63","author":"Xu","year":"2003","journal-title":"Kidney Int."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Pan, W., Yu, H., Huang, S., and Zhu, P. (2016). Resveratrol Protects against TNF-\u03b1-Induced Injury in Human Umbilical Endothelial Cells through Promoting Sirtuin-1-Induced Repression of NF-KB and p38 MAPK. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147034"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4398","DOI":"10.21037\/jtd.2017.09.135","article-title":"Urban particulate matter triggers lung inflammation via the ROSMAPK- NF-\u03baB signaling pathway","volume":"9","author":"Wang","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S1734-1140(09)70111-2","article-title":"Role of NF-\u03baB in the pathogenesis of diabetes and its associated complications","volume":"61","author":"Patel","year":"2009","journal-title":"Pharmacol. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1128\/IAI.01412-06","article-title":"p38 Mitogen-Activated Protein Kinase Controls NF-\u03baB Transcriptional Activation and Tumor Necrosis Factor Alpha Production through RelA Phosphorylation Mediated by Mitogen- and Stress-Activated Protein Kinase 1 in Response to Borrelia burgdorferi Antigens","volume":"75","author":"Olson","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7101","DOI":"10.4049\/jimmunol.179.10.7101","article-title":"MAPK p38 regulates transcriptional activity of NF-kappaB in primary human astrocytes via acetylation of p65","volume":"179","author":"Saha","year":"2007","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10556","DOI":"10.1038\/s41598-019-46794-5","article-title":"The roles of p38 MAPK\u2009\u2192\u2009COX2 and NF-\u03baB\u2009\u2192\u2009COX2 signal pathways in age-related testosterone reduction","volume":"9","author":"Zhao","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"603","DOI":"10.3892\/mmr.2013.1554","article-title":"Activation of the p38 MAPK\/NF-kappaB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells","volume":"8","author":"Guo","year":"2013","journal-title":"Mol. Med. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7233\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:26:21Z","timestamp":1760163981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":88,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22137233"],"URL":"https:\/\/doi.org\/10.3390\/ijms22137233","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,5]]}}}