Macitentan inhibits the transforming growth factor-? profibrotic action, blocking the signaling mediated by the ETR/T?RI complex in systemic sclerosis dermal fibroblasts

Systemic sclerosis (SSc) is a complex and not fully understood autoimmune disease associated with fibrosis of multiple organs. The main effector cells, the myofibroblasts, are collagen-producing cells derived from the activation of resting fibroblasts. This process is regulated by a complex repertoire of profibrotic cytokines, and among them transforming growth factor beta (TGF-?) and endothelin-1 (ET-1) play a major role. In this paper we show that TGF-? and ET-1 receptors co-operate in myofibroblast activation, and macitentan, an ET-1 receptor antagonist binding ET-1 receptors, might interfe... Mehr ...