Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy
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...
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Dove Medical Press
2021
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oai:doaj.org-article:16404d90e8b74ccda96f8cfed0b0e9132021-12-02T15:52:56ZSalusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy1178-7007https://doaj.org/article/16404d90e8b74ccda96f8cfed0b0e9132021-05-01T00:00:00Zhttps://www.dovepress.com/salusin--mediates-high-glucose-induced-inflammation-and-apoptosis-in-r-peer-reviewed-fulltext-article-DMSOhttps://doaj.org/toc/1178-7007Hao 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 zxued@sina.comBackground: 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 retinopathyWang HZhang MZhou HCao LZhou JChen QZhang XDove Medical Pressarticlesalusin-βreactive oxygen speciesinflammationapoptosisdiabetic retinopathySpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 2291-2308 (2021) |
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DOAJ |
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EN |
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salusin-β reactive oxygen species inflammation apoptosis diabetic retinopathy Specialties of internal medicine RC581-951 |
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salusin-β reactive oxygen species inflammation apoptosis diabetic retinopathy Specialties of internal medicine RC581-951 Wang H Zhang M Zhou H Cao L Zhou J Chen Q Zhang X Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy |
| description |
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 zxued@sina.comBackground: 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 |
| format |
article |
| author |
Wang H Zhang M Zhou H Cao L Zhou J Chen Q Zhang X |
| author_facet |
Wang H Zhang M Zhou H Cao L Zhou J Chen Q Zhang X |
| author_sort |
Wang H |
| title |
Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy |
| title_short |
Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy |
| title_full |
Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy |
| title_fullStr |
Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy |
| title_full_unstemmed |
Salusin-β Mediates High Glucose-Induced Inflammation and Apoptosis in Retinal Capillary Endothelial Cells via a ROS-Dependent Pathway in Diabetic Retinopathy |
| title_sort |
salusin-β mediates high glucose-induced inflammation and apoptosis in retinal capillary endothelial cells via a ros-dependent pathway in diabetic retinopathy |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/16404d90e8b74ccda96f8cfed0b0e913 |
| work_keys_str_mv |
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