SB-431542 inhibits TGF-β-induced contraction of collagen get by normal and keloid fibroblasts

Background: Transforming growth factor (TGF)-beta induces fibroblast contraction, which is implicated in wound heating and keloid formation. SB-431542 is a novel specific inhibitor of TGF-beta type I receptor kinase activity. Objective : We sought to determine whether SB-431542 inhibited TGF-beta-induced fibroblast contraction. Methods : We used an in vitro type I collagen get contraction assay with normal or keloid dermal fibroblasts incorporated. Results : TGF-beta induced contraction of collagen gets with normal dermal fibroblasts incorporated, which was efficiently suppressed by SB-431542. Keloid fibroblasts showed higher basal contraction of collagen gets in the absence of TGF-beta than normal fibroblasts, which was enhanced by addition of TGF-beta. SB-431542 suppressed both the basal and TGF-beta-enhanced contraction of collagen gets by keloid fibroblasts. These inhibitory effects of SB-431542 were associated with suppression of TGF-beta-induced alpha-smooth muscle actin (alpha-SMA) expression and phosphorylation of Smad2 in normal and keloid fibroblasts. Conclusion : SB-431542 can suppress TGF-beta-induced contraction of collagen get by normal and keloid dermal fibroblasts. Importantly, SB-431542 can inhibit basal contraction of collagen get by keloid fibroblasts. These results suggest that an inhibitor of TGF-beta type I receptor kinase activity may have therapeutic potential for excessive skin contraction as observed in keloid. (c) 2005 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All. rights reserved.