Cell-intrinsic alterations in SSc fibroblasts including deregulated TGF-β and Wnt signaling, altered expression or function of c-Abl and Egr-1; persistent TLR activation by DAMPs, hypoxia and mechanical forces and a functional deficiency of endogenous repressors of fibroblast differentiation and collagen production such as PPAR-γ and microRNAs, contribute to persistent biosynthetic and mechanical activity, and progressive fibrosis [46]. This evidence concerns the gene TGFB1 and systemic sclerosis.