The role of Gas6/MerTK/GPX4 signal pathway in iron-induced cell death in diabetic retinopathy
10.19405/j.cnki.issn1000-1492.2024.10.012
- VernacularTitle:糖尿病视网膜病变中Gas6/MerTK/GPX4信号通路参与铁诱导的细胞死亡的作用研究
- Author:
Li DENG
1
;
Ling LI
;
Jiang YUE
;
Zhengqun LIU
;
Juanping YIN
;
Xiaoli CAI
Author Information
1. 长沙市第四医院(湖南师范大学附属长沙医院)眼科,长沙 410006
- Keywords:
diabetic retinopathy;
growth arrest-specific 6;
Mer tyrosine kinase;
ferroptosis;
rat
- From:
Acta Universitatis Medicinalis Anhui
2024;59(10):1777-1784
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of growth arrest-specific 6(Gas6)/Mer tyrosine kinase(MerTK)signaling pathway in ferroptosis in diabetes retinopathy(DR).Methods Human retinal pigment epithelial cells(ARPE-19)were divided into control group,HG group,HG+sh-Gas6 group,and HG+Gas6 group.Cells were exposed to 25 mmol/L D-glucose for simulating an in vitro hyperglycemic(HG)environment.The control group was exposed to a 20 mmol/L mannitol+5.5 mmol/L glucose environment.Rats were randomly divided into normal control group,DR group,and DR+Gas6 group,with 20 rats in each group.A DR model was established by intra-peritoneal injection of STZ solution.Cell proliferation was evaluated using the cell count kit 8(CCK-8)assay.Lip-id reactive oxygen species(ROS)levels were measured by flow cytometry,and levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)were measured by biochemical assays to eval-uate iron death.The expression of Gas6 and MerTK proteins was analyzed by Western blot.Results Compared with HG group,the cell viability,SOD,GSH-Px levels in HG+Gas6 group increased significantly(P＜0.05),while the levels of lipid-ROS and MDA decreased significantly(P＜0.05).In HG+sh-Gas6 group,the cell via-bility,SOD and GSH-Px levels decreased significantly(P＜0.05),while the levels of lipid-ROS and MDA in-creased significantly(P＜0.05).In addition,the expression of GPX4 protein in HG+Gas6 group was significant-ly higher than that in HG group(P＜0.05),and the expression of GPX4 protein in HG+sh-Gas6 group was sig-nificantly lower than that in HG group(P＜0.05).Compared with the control group,the average thickness of reti-nal nerve fiber layer in DR group significantly decreased(P＜0.05),while that in DR+Gas6 group increased sig-nificantly(P＜0.05).In addition,the levels of MDA and iron in retinal pigment epithelium(RPE)tissues of DR+Gas6 group decreased significantly(P＜0.05),while the levels of GSH and the expressions of Gas6,MerTK and GPX4 proteins increased significantly(P＜0.05).Conclusion HG treatment accelerates the clearance of GPX4 by inhibiting the Gas6/MerTK signaling pathway,inducing ferroptosis and cell growth inhibition in ARPE-19 cells.In addition,up-regulating the expression of Gas6/MerTK signal in DR rat retina can alleviate ferroptosis and oxidative stress in RPE tissue,and help to restore the average retinal nerve fiber layer thickness.
- Full text:2024122511565915588糖尿病视网膜病变中Gas6...铁诱导的细胞死亡的作用研究_邓里.pdf
