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2017 ; 8
(47
): 82064-82077
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
MicroRNA-423-5p facilitates hypoxia/reoxygenation-induced apoptosis in renal
proximal tubular epithelial cells by targeting GSTM1 via endoplasmic reticulum
stress
#MMPMID29137244
Yuan XP
; Liu LS
; Chen CB
; Zhou J
; Zheng YT
; Wang XP
; Han M
; Wang CX
Oncotarget
2017[Oct]; 8
(47
): 82064-82077
PMID29137244
show ga
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.