YB-1 mediates IFN-γ dependent regulation of TGF-β responsive genes, thereby providing antifibrotic effects

Abstract

Hepatic stellate cells (HSC) are the main producers of type I collagen (Col1) in normal and cirrhotic liver. The function of TGF-b as profibrogenic cytokine and inducer of collagen expression has been exploited in TGF-b antagonizing strategies to experimentally reduce collagen content and fibrogenesis. In HSC, Smads3/4 mediate the TGF-b effect to the collagen promoter, which can be abrogated in vitro and in vivo by inhibitory Smad7. In various cell types, Y-box protein 1 also interferes with the collagen promoter and represses collagen synthesis.