Identification of Id1 as target gene of profibrogenic TGF-β family signaling during transdifferentiation of hepatic stellate cells

Members of the Id subfamily of helix-loop-helix (HLH) proteins are involved in regulation of cellular proliferation and differentiation by inhibiting DNA-binding activity of basic-HLH (bHLH) proteins. In the present study we demonstrate upregulation of Id1 protein expression in hepatic stellate cells (HSC) after stimulation with TGF-β. This cytokine is essential for HSC transdifferentiation and mediates liver fibrosis in vivo. Overexpression of Smad7, an intracellular antagonist of TGF-β signal transduction, significantly suppressed transdifferentiation of HSC, „freezing“ the cells in a quiescent stage. Addition…