title: Advanced oxidation protein products induce endothelial-to-mesenchymal transition in human renal glomerular endothelial cells through induction of endoplasmic reticulum stress.
abstract: Endothelial-to-mesenchymal transition (EndMT) in renal glomerular endothelial cells plays a critical role in the pathogenesis of diabetic nephropathy (DN). Furthermore, advanced oxidation protein products (AOPPs) have been shown to contribute to the progression of DN. However, whether AOPPs induce EndMT in renal glomerular endothelial cells remains unclear. Thus, we investigated the effect of AOPPs on human renal glomerular endothelial cells (HRGECs) and the mechanisms underlying the effects. Our results showed that AOPP treatment lowered the expression of vascular endothelial cadherin, CD31, and claudin 5 and induced the overexpression of α-smooth muscle actin, vimentin, and fibroblast-specific protein 1, which indicated that AOPPs induced EndMT in HRGECs. Furthermore, AOPP stimulation increased the expression of glucose-regulated protein 78 and CCAAT/enhancer-binding protein-homologous protein, which suggested that AOPPs triggered endoplasmic reticulum (ER) stress in HRGECs. Notably, the aforementioned AOPP effects were reversed following the treatment of cells with salubrinal, an inhibitor of ER stress, whereas the effects were reproduced after exposure to thapsigargin, an inducer of ER stress. Collectively, our results indicate that AOPPs trigger EndMT in HRGECs through the induction of ER stress. These findings suggest novel therapeutic strategies for inhibiting renal fibrosis by targeting ER stress.
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China.
authors: Xiujie
authors: X
authors: Liang
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China.
authors: Na
authors: N
authors: Duan
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China.
authors: Yue
authors: Y
authors: Wang
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China.
authors: Shuangshuang
authors: S
authors: Shu
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China.
authors: Xiaohong
authors: X
authors: Xiang
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China.
authors: Tingting
authors: T
authors: Guo
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China.
authors: Lei
authors: L
authors: Yang
authors: College of Arts and Science, Syracuse University, Syracuse, NY, USA.
authors: Shaojie
authors: S
authors: Zhang
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China. Electronic address: 1847672118@qq.com.
authors: Xun
authors: X
authors: Tang
authors: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China. Electronic address: gzh_zj@qq.com.
authors: Jun
authors: J
authors: Zhang
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology; D003928:Diabetic Nephropathies / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D018384:Oxidative Stress / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D062107:Advanced Oxidation Protein Products; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D002934:Cinnamates; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C496827:salubrinal; D019284:Thapsigargin; C019363:eIF-2 phosphatase; D010749:Phosphoprotein Phosphatases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013890:Thiourea
keywords: Advanced oxidation protein products (AOPPs); Diabetic nephropathy (DN); Endoplasmic reticulum (ER) stress; Endothelial-to-mesenchymal transition (EndMT); Human renal glomerular endothelial cells