Salusin-Βeta Upregulation Activates High Glucose-induced Inflammation And Apoptosis In Human Retinal Capillary Endothelial Cells And Exacerbates Diabetic Retinopathy Via Ros-dependent JNK And P38 Mapk Signalling

Background: Diabetic retinopathy(DR)is characterized by retinal vascular endothelial cell death and vascular inflammation,which are microvascular complications of diabetes mellitus(DM)induced by long-term hyperglycaemia.Salusin-β,a newly identified peptide,is closely associated with hypertension,atherosclerosis,diabetic cardiomyopathy and acute kidney injury.However,the exact role of salusin-β in hyperglycaemia-induced retinal capillary endothelial cell(REC)inflammation and apoptosis are still unclear.Patients and methods: A total of 60 patients with type 2 diabetes and20 healthy controls were included in this study.According to fundus fluorescein angiography,the diabetes patients were divided into three subgroups: no DR,non-proliferative DR(NPDR)and proliferative DR(PDR).Serum salusin-β levels were measured by enzyme-linked immunosorbent assay.Human retinal capillary endothelial cell(HRECs)were cultured in normal glucose(NG),high glucose(HG)with or without salusin-β.Salusin-β expression was examined by Western blotting and immunofluorescence staining.Expression of the pro-inflammatory cytokines MCP-1,IL-1β,TNF-α,and VCAM-1 was measured by Western blotting.Reactive oxygen species(ROS)production was measured by2′,7′-dichlorofluorescein diacetate(DCFH-DA).Cell apoptosis rates were determined by flow cytometry.The expression of p38,JNK,p-p38,and p-JNK and the apoptosis-related proteins cleaved caspase3,Bax,and Bcl2 were measured by Western blotting.Results: Serum salusin-β levels were higher in diabetes patients than in healthy controls(p = 0.0027),especially in patients with NPDR and PDR(p<0.01,both).HG upregulated salusin-β expression in HRECs in a time-dependent manner.Salusin-β exacerbated inflammation and apoptosis,upregulated intracellular ROS in HG-induced HRECs,and activated ROS-dependent JNK and p38 MAPK signalling.Conclusion: Our findings indicated that salusin-β could promote inflammation and apoptosis via ROS-dependent JNK and p38 MAPK signalling in HG-induced HRECs and could be a therapeutic target for DR.