We demonstrated previously that because of the Smad7 deficiency and increased Smad3 expression in SSc fibroblasts, transplantation of SSc skin retained the SSc phenotype in SCID mice, indicating that the altered balance between positive and inhibitory Smads may represent an intrinsic defect in tissue fibroblasts that can maintain or even induce SSc lesions autonomously in the absence of altered circulatory or systemic factors [9]. This evidence concerns the gene SMAD3 and systemic sclerosis.