Somyoth Sridurongrit, Chen Ke, Wanthita Kongphat, Arnon Pudgerd, and Chanyatip Suwannasing

DOI: 10.14456/sjst-psu.2018.31

pp. 314 - 320

Abstract

While transforming growth factor-β (TGF-β) is known to be a key inducer of hepatic stellate cell (HSC) activation
during liver fibrosis but it is unclear which TGF-β receptor is required for this HSC-mediated fibrogenesis. Here, we report that
abrogation of TGF-β type I receptor ALK5 in HSC activation led to reduced collagen deposition and a decreased number of
myofibroblasts in livers of mutant mice lacking ALK5 in HSC (Alk5/GFAP-Cre mice) following thioacetamide (TAA) exposure.
The reduced fibrosis was accompanied by decreased expression of HSC activation markers in livers. In addition, Alk5/GFAP-Cre
mice exhibited decreased immune cell infiltration and reduced production of inflammatory cytokines. Associated with reduced
fibrosis and inflammation, amelioration of liver injury was observed in Alk5/GFAP-Cre mice after TAA treatment. In conclusion,
our results indicated that TGF-β signaling via ALK5 in HSC enhanced liver fibrogenesis and inflammation led to amplification
of hepatic injury in mice exposed to TAA.