Transforming growth factors β1, β2, and β3 and their receptors are differentially regulated during normal and impaired wound healing

Abstract

A series of studies has shown that application of transforming growth factor β (TGF-β) to a wound has a beneficial effect, especially in animals with wound healing disorders. In this study we have investigated the regulation of TGF-β1,β2, and β3 and their receptors during the repair process. We found a large induction of all three TGF-β isoforms and also of TGF-β types I and II receptors, although the time course of induction and the absolute expression levels were different for these genes. Furthermore, each TGF-β isoform had distinct sites of expression in the wound. Systemic treatment with glucocorticoids significantly altered the expression levels of TGF-βs and TGF-β receptors. Whereas expression of TGF-β1, TGF-β2, and TGF-β type II receptor was suppressed by glucocorticoids in normal and wounded skin, expression of TGF-β3 and TGF-β receptor type I mRNA was stimulated. These findings provide an explanation for the beneficial effect of exogenous TGF-β in the treatment of impaired wound healing in glucocorticoid-treated animals. Furthermore, they suggest that a disturbed balance between the levels of the three TGF-β isoforms and their receptors might underlie the wound healing defect seen in glucocorticoid-treated animals.