Transforming growth factor-β1-mediated collagen gel contraction by cardiac fibroblasts

OBJECTIVE: Myofibroblasts and transforming growth factor-beta(1) (TGF-beta(1)) are key elements of cardiac tissue fibrosis development. The aim of this study was to determine whether the ability of TGF-beta(1) to affect the contractile activity of cardiac fibroblasts depends on their differentiation into myofibroblasts. METHODS: Cardiac fibroblasts (from male adult Wistar rats) from passage two were cultured to confluency and incubated on a hydrated collagen gel with and without TGF-beta(1) (0, 20, 40, 100, 200, 400 or 600 pmol/L) for one, two and three days in a Dulbecco's Modified Eagle's Medium without foetal bovine serum. RESULTS: TGF-beta(1) dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100 pmol/L TGF-beta(1). TGF-beta(1) also stimulated 3(H)-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice. TGF-beta(1) dose-dependently induced an increase in beta-smooth muscle actin, a marker of myofibroblasts. The TGF-beta(1)-induced reduction of area of the collagen gel was negatively correlated to the TGF-beta(1)-evoked appearance of a-smooth muscle actin in the collagen gel matrix. CONCLUSION: Our data demonstrate that TGF-beta(1) increased the contractile activity of adult rat cardiac fibroblasts and their ability to differentiate into myofibroblasts. Because contractile activity was correlated with differentiation, the influence of TGF-beta(1) on cardiac fibroblast-induced collagen gel contraction might depend on the promotion of myofibroblast differentiation.