Diversity of TGF-β-signaling in rat hepatic stellate cells and in myofibroblasts

Aims: TGF-β is the major cytokine regulating hepatic stellate cell (HSC) function in the course of liver fibrogenesis. We priviously have shown that HSC express beside the „classical“ TGF-β sensors, i.e. ALK5 (type I receptor), RII (type II receptor) and betaglycan (type III receptor), endoglin an alternative type III receptor [1]. Endoglin is able to modulate TGF-β responses either via the classical pathway [2] or an accessory TGF-β pathway [3]. Here we show that the components of the accessory signaling branche, i.e. ALK1 (type I receptor) as well as the "BMP"-Smads1, 5 and 8, are expressed in HSC and transdifferentiated myofibroblasts. Furthermore we show that this signaling pathway is activated in a time and dose dependent manner which is different from the classical pathway.