C/EBP homologous protein (CHOP) deficiency ameliorates renal fibrosis in unilateral ureteral obstructive kidney disease

// Shing-Hwa Liu 1, 2, 3, * , Cheng-Tien Wu 1, * , Kuo-How Huang 4, * , Ching-Chia Wang 2 , Siao-Syun Guan 5 , Li-Ping Chen 6 , Chih-Kang Chiang 1 , 7 1 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 2 Department of Pediatrics, College of Medicine, National Taiwan University & Hospital, Taipei, Taiwan 3 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 4 Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan 5 Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan 6 Department of Dentistry, Taipei Chang Gang Memorial Hospital, Chang Gang University, Taipei, Taiwan 7 Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Chih-Kang Chiang, e-mail: ckchiang@ntu.edu.tw Keywords: CHOP, renal fibrosis, unilateral ureteral obstruction, oxidative stress Received: January 07, 2016     Accepted: February 23, 2016     Published: March 03, 2016 ABSTRACT 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.