期刊
JOURNAL OF DIABETES AND ITS COMPLICATIONS
卷 30, 期 4, 页码 573-579出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jdiacomp.2016.01.009
关键词
Advanced oxidation protein products (AOPPs); Endoplasmic reticulum (ER) stress; Endothelial-to-mesenchymal transition (EndMT); Human renal glomerular endothelial cells; Diabetic nephropathy (DN)
资金
- Natural Science Foundation of Guangdong Province [10151051501000030, S2011010004053, S2011040003566]
- Science and Technical Plan of Guangzhou, Guangdong, China [11C22120703]
- Science and Technical Plan of Guangdong, China [2013B021800149]
- National Natural Science Foundation of China [81202842]
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 alpha-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. (C) 2016 Elsevier Inc. All rights reserved.
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