Transforming Growth Factors b1, b2, and b3 and Their Receptors Are Differentially Regulated during Normal and Impaired Wound Healing*

A series of studies has shown that application of transforming growth factor b (TGF-b) to a wound has a beneficial effect, especially in animals with wound healing disorders. In this study we have investigated the regulation of TGF-b1, b2, and b3 and their receptors during the repair process. We found a large induction of all three TGF-b isoforms and also of TGF-b types I and II receptors, although the time course of induction and the absolute expression levels were different for these genes. Furthermore, each TGF-b isoform had distinct sites of expression in the wound. Systemic treatment with glucocorticoids significantly altered the expression levels of TGF-bs and TGF-b receptors. Whereas expression of TGF-b1, TGF-b2, and TGF-b type II receptor was suppressed by glucocorticoids in normal and wounded skin, expression of TGF-b3 and TGF-b receptor type I mRNA was stimulated. These findings provide an explanation for the beneficial effect of exogenous TGF-b 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-b isoforms and their receptors might underlie the wound healing defect seen in glucocorticoidtreated animals.