The first study of the anti-fibrotic effect of bosentan on SSc fibroblasts was reported in 2004 by Shi-Wen et al. A series of studies from their group demonstrated that bosentan suppresses the expression of α-SMA, type I collagen, fibronectin, and CCN2 in SSc lung fibroblasts and ET-1 is a downstream mediator of pro-fibrotic responses to TGF-β in human lung fibroblasts [8,10,11]. This evidence concerns the gene EDN1 and systemic sclerosis.