EDN1 and systemic sclerosis: ET-1 induces a pro-fibrotic phenotype in fibroblasts through increasing the expression of extracellular matrix (ECM) proteins, such as type I and III collagen and fibronectin, and decreasing the expression of matrix metalloproteinase 1 [39,40], therefore the blockade of ET-1 signaling has been thought to be a potential therapeutic strategy for fibrotic disorders, including SSc.