MicroRNA-423-5p facilitates hypoxia/reoxygenation-induced apoptosis in renal proximal tubular epithelial cells by targeting GSTM1 via endoplasmic reticulum stress
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Xiao-Peng Yuan1, Long-Shan Liu2, Chuan-Bao Chen1, Jian Zhou1, Yi-Tao Zheng1, Xiao-Ping Wang1, Ming Han1 and Chang-Xi Wang2
13rd Division of Organ Transplant Center, Eastern Campus of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P.R. China
22nd Division of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R. China
Xiao-Peng Yuan, email: [email protected]
Keywords: MicroRNA-423-5p, GSTM1, renal proximal tubule epithelial cells, epithelial cell repair, endoplasmic reticulum stress
Received: February 24, 2017 Accepted: May 06, 2017 Published: May 30, 2017
It has been reported that microRNAs (miRs) can regulate renal response to acute injury and members of them are believed to be important in maintenance of renal function and development of renal injury. We investigated the actions of microRNA-423-5p (miR-423-5p) and glutathione-S-transferase (GST) M1 after acute kidney injury. MiR-423-5p was up-regulated and GSTM1 was down-regulated in human kidney (HK-2) cells subjected to hypoxia/reoxygenation (H/R) and in rat kidneys subjected to ischemia/reperfusion (I/R) injury. Dual luciferase assays revealed miR-423-5p binding to the 3′ untranslated region of GSTM1. Proliferation was lower and apoptosis, ER stress and oxidative stress were all higher in H/R-treated HK-2 cells transfected with or without miR-423-5p mimics and GSTM1 siRNA than in the same cells transfected with miR-423-5p inhibitors and a GSTM1 expression vector. Increased miR-423-5p and decreased GSTM1 mRNA and protein levels were observed in rat kidneys on days 1, 2 and 7 after I/R. Levels had normalized by days 14 and 21. On day 3 after treatment, rats receiving I/R or I/R plus miR-423-5p mimics exhibited higher serum creatinine and urea nitrogen levels than rats receiving I/R plus a miR-423-5p inhibitor. MiR-423-5p and lower GSTM1 mRNA and protein levels were higher in the I/R and I/R plus miR-423-5p mimic groups than in the I/R plus miR-423-5p inhibitors group. These findings demonstrate that after acute kidney injury, miR-423-5p induces ER stress and oxidative stress by inhibiting GSTM1and suppresses repair.
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