Fibroblast growth factor 21 attenuates oxidative stress injury in retinal pigment epithelial cells under high glucose via FGFR1/PI3K/Akt signal pathway
10.3980/j.issn.1672-5123.2026.3.04
- VernacularTitle:FGF21通过FGFR1/PI3K/Akt通路减轻高糖下视网膜色素上皮细胞的氧化应激损伤
- Author:
Ye TIAN
1
;
Guoheng ZHANG
1
;
Tianhao YUAN
1
;
Xin WANG
1
;
Tianfang CHANG
1
;
Yuan CHEN
1
;
Guorui DOU
1
Author Information
1. Department of Ophthalmology, Xijing Hospital, Air Force Medical University;Eye Institute of PLA, Xi'an 710032, Shaanxi Province, China; Department of Medical Service, Fujian Provincial Armed Police Corps Hospital, Fuzhou 350001, Fujian Province, China
- Publication Type:Journal Article
- Keywords:
retinal pigment epithelial cells;
high glucose;
oxidative stress;
single-cell RNA sequencing;
fibroblast growth factor 21(FGF21);
transcriptome sequencing;
PI3K/Akt signal pathway
- From:
International Eye Science
2026;26(3):383-390
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.
