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

Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven (K.U.Leuven), Belgium, paul.lijnen{at}med.kuleuven.ac.be

Victor Petrov

Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven (K.U.Leuven), Belgium

Robert Fagard

Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven (K.U.Leuven), Belgium

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-β 1 also stimulated ³H-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice . TGF-β ₁ dose-dependently induced an increase in smooth muscle actin, a marker of myofibroblasts. The TGF-β₁-induced reduction of area of the collagen gel was negatively correlated to the TGF- R β ₁-evoked appearance of -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.

Key Words: collagen • transforming growth factor β1 • cardiac fibroblasts • myofibroblasts • gel contraction

Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 2, 113-118 (2003)
DOI: 10.3317/jraas.2003.011


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