Down-regulation of SETD6 protects podocyte against high glucose and palmitic acid-induced apoptosis, and mitochondrial d
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ORIGINAL PAPER
Down-regulation of SETD6 protects podocyte against high glucose and palmitic acid-induced apoptosis, and mitochondrial dysfunction via activating Nrf2-Keap1 signaling pathway in diabetic nephropathy Xiang Wang1,2 · Qiling Liu1 · Deqin Kong1 · Zi Long1 · YuFang Guo2 · Shuang Wang2 · Rui Liu1 · Chunxu Hai1 Received: 16 February 2020 / Accepted: 9 August 2020 © Springer Nature B.V. 2020
Abstract Diabetic nephropathy (DN), a serious complication of hyperglycemia, is one of the most common causes of end-stage renal disease (ESRD). Glomerular podocyte injury is a major mechanism that leads to DN. However, the mechanisms underlying podocyte injury are ambiguous. In this study, we sought to investigate the contribution of SET domain-containing protein 6 (SETD6) to the pathogenesis of podocyte injury induced by glucose (GLU) and palmitic acid (PA), as well as the underlying mechanisms. Our results showed that GLU and PA treatment significantly decreased SETD6 expression in mouse podocytes. Besides, Cell Counting Kit-8 (CCK-8) and flow cytometry assay demonstrated that silencing of SETD6 silence obviously enhanced cell viability, and suppressed apoptosis in GLU and PA-induced podocytes. We also discovered that downregulation of SETD6 suppressed GLU and PA-induced ROS generation and podocyte mitochondrial dysfunction. Nrf2-Keap1 signaling pathway was involved in the effect of SETD6 on mitochondrial dysfunction. Taken together, silencing of SETD6 protected mouse podocyte against apoptosis and mitochondrial dysfunction through activating Nrf2-Keap1 signaling pathway. Therefore these data provide new insights into new potential therapeutic targets for DN treatment.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10735-020-09904-6) contains supplementary material, which is available to authorized users. * Rui Liu [email protected] * Chunxu Hai cx‑[email protected] 1
Department of Toxicology, The Ministry of Education, Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, School of Public Health, Air Force Medical University (Fourth Military Medical University), 127 Changle Western Road, Xi’an 710032, Shaanxi, People’s Republic of China
Department of Physiopathology, Xi’an Medical University, Xi’an 710021, Shaanxi, People’s Republic of China
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Vol.:(0123456789)
Journal of Molecular Histology
Graphic abstract
Keywords SET domain-containing protein 6 · Nrf2-Keap1 signaling pathway · Podocytes · Mitochondrial dysfunction · Inflammation
Introduction Diabetic nephropathy (DN) is one of the major chronic complications of diabetes (Cao and Cooper 2011). It is widely acknowledged that DN is the leading cause of end-stage renal disease (ESRD) (Bommer 2001). Hyperglycemia and hyperlipidemia can cause glomerular basement membrane thickening, mesangial expansion, and extracellular matrix hyperplasia in DN patients, further leading to glomerular hyperfiltration, p
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