C/EBP homologous protein (CHOP) deficiency ameliorates renal fibrosis in unilateral ureteral obstructive kidney disease
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Shing-Hwa Liu1,2,3,*, Cheng-Tien Wu1,*, Kuo-How Huang4,*, Ching-Chia Wang2, Siao-Syun Guan5, Li-Ping Chen6, Chih-Kang Chiang1,7
1Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
2Department of Pediatrics, College of Medicine, National Taiwan University & Hospital, Taipei, Taiwan
3Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
4Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan
5Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan
6Department of Dentistry, Taipei Chang Gang Memorial Hospital, Chang Gang University, Taipei, Taiwan
7Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan
*These authors have contributed equally to this work
Chih-Kang Chiang, e-mail: [email protected]
Keywords: CHOP, renal fibrosis, unilateral ureteral obstruction, oxidative stress
Received: January 07, 2016 Accepted: February 23, 2016 Published: March 03, 2016
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.
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