Transforming growth factor-beta 1-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.