MicroRNA-223 restricts liver fibrosis by inhibiting the TAZ-IHH-GLI2 and PDGF signaling pathways via the crosstalk of multiple liver cell types
Xiaolin Wang, Wonhyo Seo, Seol Hee Park, Yaojie Fu, Seonghwan Hwang, Robim M. Rodrigues, Dechun Feng, Bin Gao, Yong He
Abstract
Background & Aims: Liver fibrosis is a common consequence of chronic liver injury and is characterized by the accumulation of extracellular matrix mainly generated from activated hepatic stellate cells (HSCs). At present, the mechanisms underlying liver fibrogenesis remain obscure and effective pharmacological therapies are lacking. plays an important role in controlling the development of various liver diseases; however, its role in HSC activation and liver fibrosis remains unclear. Methods: Liver fibrosis was induced by chronic carbon tetrachloride (CCl4) injection of miR-223 knockout (miR-223KO) mice and littermate wild-type controls. MiR-223 was overexpressed in cultured HSCs to determine its function and targets during HSC activation and proliferation. The expression of miR-223 and pri-miR-223 was examined in primary HSCs isolated from CCl4-treated mice and in cultured HSCs. The communication between HSCs and neutrophils was studied by performing in vitro co-culture experiments.