TRANSFORMING GROWTH-FACTORS BETA-1, BETA-2, AND BETA-3 AND THEIR RECEPTORS ARE DIFFERENTIALLY REGULATED DURING NORMAL AND IMPAIRED WOUND-HEALING

A series of studies has shown that application of transforming growth factor beta (TGF-beta) to a wound has a beneficial effect, especially in animals with wound healing disorders. In this study we have investi gated the regulation of TGF-beta 1, beta 2, and beta 3 and their recep tors during the repair process. We found a large induction of all thre e TGF-beta isoforms and also of TGF-beta types I and II receptors, alt hough the time course of induction and the absolute expression levels were different for these genes. Furthermore, each TGF-beta isoform had distinct sites of expression in the wound. Systemic treatment with gl ucocorticoids significantly altered the expression levels of TGF-beta s and TGF-beta receptors. Whereas expression of TGF-beta 1, TGF-beta 2 , and TGF-beta type II receptor was suppressed by glucocorticoids in n ormal and wounded skin, expression of TGF-beta 3 and TGF-beta receptor type I mRNA was stimulated. These findings provide an explanation for the beneficial effect of exogenous TGF-beta in the treatment of impai red wound healing in glucocorticoid-treated animals. Furthermore, they suggest that a disturbed balance between the levels of the three TGF- beta isoforms and their receptors might underlie the wound healing def ect seen in glucocorticoid-treated animals.