Considering the role of TGF-β and PDGF in the human skin fibroblasts’ activation through non-SMAD signaling and induction of collagen type I, FN, α-SMA, and ROS production; the differentiation of different cells including fibroblasts and epithelial and endothelial cells to myofibroblasts (50); and the role of Ras/ERK signaling in ROS production and induction of fibrosis and EMT, it seems that TGF-β and PDGF act in SSc pathogenesis partly through activation of the Ras/ERK pathway. This evidence concerns the gene TGFB1 and systemic sclerosis.