These results indicate that the impaired Smad7-Smurf-mediated inhibitory effect on TGF-beta signaling might contribute to maintaining the autocrine TGF-beta loop in scleroderma fibroblasts.
Protein and mRNA levels of SMAD3, but not of SMAD4 or SMAD7, were variably elevated in scleroderma fibroblasts compared with those from healthy controls.
Recent reports have implicated Smad7 as a crucial regulator of TGF-beta activity in human disease; aberrant expression of Smad7 is involved in inflammatory bowel disease and scleroderma.