Despite these studies implicating dysregulation of TGF-β signaling in mediating the induction of fibrosis in SSc, therapeutic approaches aimed at inhibition of TGF-β signaling have not been successful, largely owing to serious side effects caused by inhibition of the multiple pleiotropic effects of TGF-β as well as by crosstalk with numerous associated molecular signaling pathways. This evidence concerns the gene TGFB1 and systemic sclerosis.