Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts

Abstract

Granulation tissue fibroblasts (myofibroblasts) develop several ultrastructural and biochemical features of smooth muscle (SM) cells, including the presence of microfilament bundles and the expression of α-SM actin, the actin isoform typical of vascular SM cells. Myofibroblasts have been proposed to play a role in wound contraction and in retractile phenomena observed during fibrotic diseases. We show here that the subcutaneous administration of transforming growth factor-β1 (TGFβ1) to rats results in the formation of a granulation tissue in which α-SM actin expressing myofibroblasts are particularly abundant. Other cytokines and growth factors, such as platelet-derived growth factor and tumor necrosis factor-α, despite their profibrotic activity, do not induce α-SM actin in myofibroblasts. In situ hybridization with an α-SM actin probe shows a high level of α-SM actin mRNA expression in myofibroblasts of TGFβ1-induced granulation tissue. Moreover, TGFβ1 induces α-SM actin protein and mRNA expression in growing and quiescent cultured fibroblasts and preincubation of culture medium containing whole blood serum with neutralizing antibodies to TGFβ1 results in a decrease of α-SM actin expression by fibroblasts in replicative and non-replicative conditions. These results suggest that TGFβ1 plays an important role in myofibroblast differentiation during wound healing and fibrocontractive diseases by regulating the expression of α-SM actin in these cells.