Beneficial Effects of Fibroblast Growth Factor-1 on Retinal Pigment Epithelial Cells Exposed to High Glucose-Induced Damage: Alleviation of Oxidative Stress, Endoplasmic Reticulum Stress, and Enhancement of Autophagy

• Published in: International journal of molecular sciences Vol. 25; no. 6; p. 3192
• Main Authors: Huang, Hsin-Wei, Yang, Chung-May, Yang, Chang-Hao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2024; MDPI
• Subjects: adenosine monophosphate-activated protein kinase; Apoptosis; Autophagy; Breath tests; Cell death; Dextrose; Diabetes; Diabetic retinopathy; Endoplasmic reticulum; endoplasmic reticulum stress; Enzymes; fibroblast growth factor-1; Fibroblast growth factors; Fibroblasts; Glucose; Growth factors; Hyperglycemia; Insulin; Kinases; Lipid peroxidation; Metabolism; Oxidative stress; Pathophysiology; Physiology; Protein folding; Massachusetts; Taiwan; mammalian target of rapamycin; autophagy; fibroblast growth factor-1; adenosine monophosphate-activated protein kinase; diabetic retinopathy; endoplasmic reticulum stress; oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25063192

Diabetic retinopathy (DR) severely affects vision in individuals with diabetes. High glucose (HG) induces oxidative stress in retinal cells, a key contributor to DR development. Previous studies suggest that fibroblast growth factor-1 (FGF-1) can mitigate hyperglycemia and protect tissues from HG-induced damage. However, the specific effects and mechanisms of FGF-1 on DR remain unclear. In our study, FGF-1-pretreated adult retinal pigment epithelial (ARPE)-19 cells were employed to investigate. Results indicate that FGF-1 significantly attenuated HG-induced oxidative stress, including reactive oxygen species, DNA damage, protein carbonyl content, and lipid peroxidation. FGF-1 also modulated the expression of oxidative and antioxidative enzymes. Mechanistic investigations showed that HG induced high endoplasmic reticulum (ER) stress and upregulated specific proteins associated with apoptosis. FGF-1 effectively alleviated ER stress, reduced apoptosis, and restored autophagy through the adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin signaling pathway. We observed that the changes induced by HG were dose-dependently reversed by FGF-1. Higher concentrations of FGF-1 (5 and 10 ng/mL) exhibited increased effectiveness in mitigating HG-induced damage, reaching statistical significance ( < 0.05). In conclusion, our study underscores the promising potential of FGF-1 as a safeguard against DR. FGF-1 emerges as a formidable intervention, attenuating oxidative stress, ER stress, and apoptosis, while concurrently promoting autophagy. This multifaceted impact positions FGF-1 as a compelling candidate for alleviating retinal cell damage in the complex pathogenesis of DR.