Diabetes, Metabolic Syndrome and Obesity (May 2021)
Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy
Abstract
Hao Wang,1– 3 Meng Zhang,1,3 Hongli Zhou,1,3 Lang Cao,1,3 Jie Zhou,1,3 Qinyun Chen,1,3 Xuedong Zhang1,3 1Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Ophthalmology, Fuling Center Hospital of Chongqing City, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, People’s Republic of ChinaCorrespondence: Xuedong ZhangDepartment of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, People’s Republic of ChinaEmail [email protected]: Diabetic retinopathy (DR) is characterized by retinal vascular endothelial cell death and vascular inflammation, which are microvascular complications of diabetes mellitus (DM). Salusin-β, a newly identified peptide, is closely associated with hypertension, atherosclerosis and diabetic cardiomyopathy. However, the exact role of salusin-β in high glucose (HG)-induced retinal capillary endothelial cell (REC) inflammation and apoptosis remains unclear.Patients and Methods: A total of 60 patients with type 2 diabetes and 20 healthy controls were included in this study. Based on fundus fluorescein angiography findings, the diabetic patients were divided into three subgroups: diabetes without retinopathy (DWR), non-proliferative DR (NPDR) and proliferative DR (PDR). Serum salusin-β levels were measured by enzyme-linked immunosorbent assay. Human RECs (HRECs) were cultured in normal glucose (NG) and HG medium with or without salusin-β. Salusin-β expression was analysed by Western blotting and immunofluorescence staining. Expression of the pro-inflammatory cytokines MCP-1, IL-1β, TNF-α, and VCAM-1 was analysed by Western blotting. Reactive oxygen species (ROS) production was measured with 2′,7′-dichlorofluorescein diacetate (DCFH-DA). Cell apoptosis rates were determined by flow cytometry. The levels of p38, JNK, p-p38, and p-JNK and the apoptosis-related proteins cleaved caspase-3, Bax, and cl2 were analysed by Western blotting.Results: Serum salusin-β levels were higher in diabetic patients than in healthy controls (p = 0.0027), especially in patients with NPDR and PDR (both p< 0.01). HG upregulated salusin-β expression in HRECs in a time-dependent manner. Salusin-β exacerbated inflammation and apoptosis, upregulated intracellular ROS production in HG-induced HRECs, and activated ROS-dependent JNK and p38 MAPK signalling, while knockdown of salusin-β suppressed these effects.Conclusion: Our findings indicate that salusin-β can promote inflammation and apoptosis via ROS-dependent JNK and p38 MAPK signalling in HG-induced HRECs and could be a therapeutic target for DR.Keywords: salusin-β, reactive oxygen species, inflammation, apoptosis, diabetic retinopathy
