Suppression of the production of extracellular matrix and α-smooth muscle actin induced by transforming growth factor-β1 in fibroblasts of the flexor tendon sheath by hepatocyte growth factor

We examined the effectiveness of hepatocyte growth factor (HGF) in blocking production of transforming growth factor (TGF)-beta 1-induced collagen I, fibronectin, and alpha-smooth muscle actin (alpha-SMA) in the flexor tendon sheath of rabbits in vitro. Fibroblasts were obtained from the sheaths. Cell culture was supplemented with TGF-beta 1 5 ng/ml and increasing doses of HGF (10-40 ng/ml). The production of collagen I and fibronectin in supernatants culture were examined using an enzyme-linked immunosorbent assay (ELISA). alpha-SMA expression was assessed by western blot. TGF-beta 1 stimulated production of collagen I, fibronectin, and alpha-SMA greatly, while HGF significantly (p < 0.05) reduced production of all components induced by TGF-beta 1 in a dose-dependent manner. This suggests that HGF effectively antagonises the action of TGF-beta 1 in cultured fibroblasts from flexor tendon sheaths. The results provide a cellular and molecular basis for HGF acting as a therapeutic agent for adhesions in flexor tendons.