On the one hand, ALK1/Smad1/Smad5 signaling pathway can regulate the profibrotic phenotype in SSc fibroblasts, leading to the increased production of ECM components, such as type I collagen and connective tissue growth factor (CTGF) (Pannu et al., 2007, 2008). This evidence concerns the gene ACVRL1 and systemic sclerosis.