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MicroRNA-423-5p facilitates hypoxia/reoxygenation-induced apoptosis in renal proximal tubular epithelial cells by targeting GSTM1 via endoplasmic reticulum stress.
Yuan, Xiao-Peng; Liu, Long-Shan; Chen, Chuan-Bao; Zhou, Jian; Zheng, Yi-Tao; Wang, Xiao-Ping; Han, Ming; Wang, Chang-Xi.
Afiliação
  • Yuan XP; 3rd Division of Organ Transplant Center, Eastern Campus of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P.R. China.
  • Liu LS; 2nd Division of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R. China.
  • Chen CB; 3rd Division of Organ Transplant Center, Eastern Campus of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P.R. China.
  • Zhou J; 3rd Division of Organ Transplant Center, Eastern Campus of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P.R. China.
  • Zheng YT; 3rd Division of Organ Transplant Center, Eastern Campus of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P.R. China.
  • Wang XP; 3rd Division of Organ Transplant Center, Eastern Campus of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P.R. China.
  • Han M; 3rd Division of Organ Transplant Center, Eastern Campus of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, P.R. China.
  • Wang CX; 2nd Division of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P.R. China.
Oncotarget ; 8(47): 82064-82077, 2017 Oct 10.
Article em En | MEDLINE | ID: mdl-29137244
ABSTRACT
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2017 Tipo de documento: Article