We have also found that inhibitory Smad7 is selectively decreased, and we and others have shown that R-Smad3 is increased, in SSc skin fibroblasts, resulting in uncontrolled TGFβ activity that may be, at least in part, responsible for the aberrant ECM deposition observed in SSc [9]. This evidence concerns the gene TGFB1 and systemic sclerosis.