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Updated: May 23, 2025

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Autocrine GDF10 Inhibits Hepatic Stellate Cell Activation via BMPR2/ALK3 Receptor to Prevent Liver Fibrosis
Yinliang Zhang1, Xiaochen Gai2, Yuhui Li1
1Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Cellular Homeostasis and Disease, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Abstract:
Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis, and their activation is controlled by a complex interplay of autocrine/paracrine signals within the liver microenvironment. Here, we show that growth differentiation factor 10 (GDF10) is specifically expressed by HSCs in both mouse and human livers, and its expression is reduced in activated HSCs. Loss of GDF10 function promotes HSC activation and exacerbates liver fibrosis in mice, while gain of GDF10 function alleviates this pathological condition. Mechanistically, autocrine GDF10 binds to BMPR2/ALK3 receptor to elicit SMAD1/5/8-SMAD7 signaling pathway in HSCs. Activated SMAD1/5/8-SMAD7 signaling pathway then inhibits the TGF-β-SMAD2/3 signaling transduction, which is essential for HSC activation. Moreover, recombinant GDF10 protein treatment suppresses HSC activation and alleviates liver fibrosis in mice. In conclusion, GDF10 is an autocrine suppressor of HSC activation and a potential therapeutic target for the treatment of liver fibrosis.
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