LY2109761 reduces TGF-β1-induced collagen production and contraction in hypertrophic scar fibroblasts

Abstract

Hypertrophic scars (HS) are fibro-hyperproliferative dermal lesions with effusive continuous accumulation of extracellular matrix components, particularly collagen. They usually occur after dermal injury in genetically susceptible individuals and cause both physical and psychological distress for the affected individuals. Transforming growth factor-β1 (TGF-β1) is known to mediate wound healing process by regulating cell differentiation, collagen production and extracellular matrix degradation. The sustained high expression of TGF-β1 is believed to result in the formation of hypertrophic scars. Inhibition of TGF-β1 signaling pathway may represent one of effective strategies for limiting excessive scarring. LY2109761, an orally active TβRI/II kinase dual inhibitor, has been previously reported that it had inhibitory effects on carcinomas and attenuates Radiation-induced pulmonary murine fibrosis. Our results revealed that LY2109761 reduced TGF-β1-induced collagen production and α-smooth muscle actin (α-SMA) expression, and attenuated TGF-β1-induced cell contraction in hypertrophic scar fibroblasts. The data from this study provide evidence supporting the potential use of LY2109761 as a novel treatment for hypertrophic scars.