Our results characterize S100A4 as a positive regulator of the stimmulatory effects of TGF-ß on fibroblasts in SSc. S100A4 is induced by TGF-ß and in turn amplifies the stimulatory effects of canonical TGF-ß / Smad signaling on collagen synthesis by SSc fibroblasts and on induction of fibrosis.
Since S100A4 is essentially required for the pro-fibrotic effects of TGF-ß and neutralizing antibodies against S100A4 are currently evaluated in tumors, S100A4 might become a candidate molecule for novel anti-fibrotic therapies.