The „accessory“ TGF-β pathway is not obligatory to ALK1 expressing cells

Aims: One of the key cytokines regulating hepatic stellate cell (HSC) function in the course of liver fibrogenesis is TGF-β [1]. In endothelial cells, TGF-β activates two interrelated Smad-dependent signaling cascades [2]. We recently found that these pathways are also present in HSC (unpublished). The "classical" pathway involves the ALK5 type I receptor which activates Smads2/3 and the "accessory" pathway transmits signals via ALK1 and Smads1/5/8 [3]. Although HSC express both type III receptors, betaglycan and endoglin, their contribution to the signaling by the ALK1 pathway is discussed controversially [4, 5]. To elucidate the role of betaglycan and endoglin in these two TGF-β signaling pathways, we utilized the myoblast cell line L6E9 as a model system [6].