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2016 ; 7
(16
): 21900-12
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C/EBP homologous protein (CHOP) deficiency ameliorates renal fibrosis in
unilateral ureteral obstructive kidney disease
#MMPMID26942460
Liu SH
; Wu CT
; Huang KH
; Wang CC
; Guan SS
; Chen LP
; Chiang CK
Oncotarget
2016[Apr]; 7
(16
): 21900-12
PMID26942460
show ga
Renal tubulointerstitial fibrosis is an important pathogenic feature in chronic
kidney disease and end-stage renal disease, regardless of the initiating insults.
A recent study has shown that CCAAT/enhancer binding protein (C/EBP) homologous
protein (CHOP) is involved in acute ischemia/reperfusion-related acute kidney
injury through oxidative stress induction. However, the influence of CHOP on
chronic kidney disease-correlated renal fibrosis remains unclear. Here, we
investigated the role of CHOP in unilateral ureteral obstruction (UUO)-induced
experimental chronic tubulointerstital fibrosis. The CHOP knockout and wild type
mice with or without UUO were used. The results showed that the increased
expressions of renal fibrosis markers collagen I, fibronectin, ?-smooth muscle
actin, and plasminogen activator inhibitor-1 in the kidneys of UUO-treated wild
type mice were dramatically attenuated in the kidneys of UUO-treated CHOP
knockout mice. CHOP deficiency could also ameliorate lipid peroxidation and
endogenous antioxidant enzymes depletion, tubular apoptosis, and inflammatory
cells infiltration in the UUO kidneys. These results suggest that CHOP deficiency
not only attenuates apoptotic death and oxidative stress in experimental renal
fibrosis, but also reduces local inflammation, leading to diminish UUO-induced
renal fibrosis. Our findings support that CHOP may be an important signaling
molecule in the progression of chronic kidney disease.