Volume 4, Number 2, June 2003

Transforming growth factor-?₁-mediated collagen gel contraction by cardiac fibroblasts
Paul Lijnen, Victor Petrov, Robert Fagard

Objective: Myofibroblasts and transforming growth factor-β₁ (TGF-β₁) are key elements of cardiac tissue fibrosis development. The aim of this study was to determine whether the ability of TGF-β₁ 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-β₁ (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-β₁ dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100 pmol/L TGF-β₁. TGF-β₁ also stimulated 3^H-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice. TGF-β₁ dose-dependently induced an increase in β-smooth muscle actin, a marker of myofibroblasts. The TGF-β₁-induced reduction of area of the collagen gel was negatively correlated to the TGF-β₁-evoked appearance of a-smooth muscle actin in the collagen gel matrix.
Conclusion: Our data demonstrate that TGF-β₁ 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-β₁ on cardiac fibroblast-induced collagen gel contraction might depend on the promotion of myofibroblast differentiation.

JRAAS 2003;4:113-118.

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