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, α-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.