• Zhuo Wei, Dan Zhao, Ye Zhang, Yuanli Chen, Shuang Zhang, Qi Li, Peng Zeng, Xiaoju Li, Wenwen Zhang, Yajun Duan, Jihong Han, and Xiaoxiao Yang.
• College of Life Science, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
• Biochem. Biophys. Res. Commun. 2019 Nov 19; 519 (4): 854-860.

AbstractLiver fibrosis is a major cause of morbidity and mortality worldwide. One of its therapeutic targets is peroxisome proliferator-activated receptor γ (PPARγ), with its ligands including rosiglitazone being tested in pre-clinical and clinical studies. However, the effects of rosiglitazone on bile duct ligation (BDL)-induced liver fibrosis and the involved mechanisms remain unknown. Herein, we used floxed control (PPARγfl/fl) and hepatocyte-specific PPARγ deficient (HepPPARγ KO) mice to conduct BDL to induce liver fibrosis and treated the animals with rosiglitazone. After one week of BDL, mice in BDL group displayed liver injury evidenced by increased collagen content, fibrosis area, necrosis area and apoptotic cells, and elevated alkaline phosphatase and alanine transaminase activities in serum. Interestingly, rosiglitazone ameliorated BDL-induced liver injury in PPARγfl/fl mice but not in HepPPARγ KO mice. Mechanistically, rosiglitazone reduced BDL-induced collagen content by downregulating fibrotic related genes including transforming growth factor β1, α-smooth muscle actin and collagen type I α1, and decreased inflammation cytokine tumor necrosis factor α level by inhibiting phosphorylation of nuclear factor-κB in a PPARγ-dependent manner. Based on findings above, we demonstrated that rosiglitazone can ameliorate BDL-induced liver fibrosis in mice and confirmed its critical functions on fibrosis by regulating NF-κB-TNF-α pathway in a PPARγ-dependent manner.Copyright © 2019 Elsevier Inc. All rights reserved.

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