Cytochrome P450 Omega-Hydroxylase 4a14 Attenuates Cholestatic Liver Fibrosis

Frontiers in Physiology

Xiaxia Zhang¹  Sha Li²  Chenghai Wang³  Wen Su⁵ 

[1] Department of Gastroenterology and Hepatology, Handan Central Hospital, Handan, China;Health Science Center, Shenzhen University, Shenzhen, China;Hebei Key Laboratory of Applied Basic Research of Blood Purification, Affiliated Hospital of Hebei Engineering University, Handan, China;Medical College, Hebei University of Engineering, Handan, China;Shenzhen Key Laboratory of Metabolism and Cardiovascular Homeostasis, Shenzhen, China;

关键词: Cyp4a14;    bile duct ligation;    liver injury;    liver fibrosis;    cholestasis;   

DOI  :  10.3389/fphys.2021.688259

来源: DOAJ

【 摘 要 】

BackgroundCholestasis is a pathological condition involving obstruction of bile secretion and excretion that results in hepatotoxicity, inflammation, fibrosis, cirrhosis, and eventually liver failure. Common bile duct ligation (BDL) model is a well-established murine model to mimic cholestatic liver fibrosis. We previously reported that cytochrome P450 omega-hydroxylase 4a14 (Cyp4a14) plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD)-related fibrosis. The goal of this study was to determine the role of Cyp4a14 in cholestatic-induced liver fibrosis.MethodsC57BL/6 mice were subjected to BDL for 14 days, and Cyp4a14 mRNA and protein levels were examined and compared with those of the sham group. Cyp4a14 knockout mice and adeno-associated virus (AAV)-mediated overexpression of Cyp4a14 in C57BL/6 mice underwent BDL and liver histology, and key fibrosis markers were examined.ResultsBoth hepatic Cyp4a14 mRNA and protein levels were markedly reduced in BDL liver compared with the time-matched sham group. Cyp4a14 gene-deficient mice aggravates whereas its overexpression alleviates BDL-induced hepatic fibrosis, which were determined by liver function, liver histology, and levels of key fibrotic markers including α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and collagen 1a2 (Col1a2).ConclusionCyp4a14 exerts a contrasting role in different hepatic fibrosis models. Strategies that enhance Cyp4a14 activity may be potential strategies to cholestatic related liver fibrosis.

【 授权许可】

Unknown