Inhibition of heme-thiolate monooxygenase CYP1B1 prevents hepatic stellate cell activation and liver fibrosis by accumulating trehalose

Authors: Hung-Chun Tung, Jong-Won Kim, Junjie Zhu, Sihan Li, Jiong Yan, Qing Liu, Imhoi Koo, Sergei A. Koshkin, Fuhua Hao, Guo Zhong, Meishu Xu, Zehua Wang, Jingyuan Wang, Yixian Huang, Yue Xi, Xinran Cai, Pengfei Xu, Songrong Ren, Takanobu Higashiyama, Frank J. Gonzalez, Song Li, Nina Isoherranen, Da Yang, Xiaochao Ma, Andrew D. Patterson, Wen Xie

Published: 2024-09-25

DOI: 10.1126/scitranslmed.adk8446

Source: Full article

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Abstract

Activation of extracellular matrix–producing hepatic stellate cells (HSCs) is a key event in liver fibrogenesis. We showed that the expression of the heme-thiolate monooxygenase cytochrome P450 1B1 (CYP1B1) was elevated in human and mouse fibrotic livers and activated HSCs. Systemic or HSC-specific ablation and pharmacological inhibition of CYP1B1 attenuated HSC activation and protected male but not female mice from thioacetamide (TAA)–, carbon tetrachloride (CCl