Wang et al. (2006) found that keloid-derived fibroblasts exposed to equibiaxial strain produce higher levels of TGF-β1, TGF-β2, and collagen 1α at mRNA and protein levels than those produced by normal skin fibroblasts. Hypoxia induces the transformation of fibroblasts into myofibroblasts by activating TGF-β/Smad3 signaling pathway and increases collagen synthesis in keloid fibroblasts in a hypertrophic keloid microenvironment induced by high matrix stiffness (Zhao et al., 2017b). This evidence concerns the gene SMAD3 and keloid.