STRONG INDUCTION OF ACTIVIN EXPRESSION AFTER INJURY SUGGESTS AN IMPORTANT ROLE OF ACTIVIN IN WOUND REPAIR

Activins are members of the transforming growth factor beta (TGF beta) superfamily, which comprises a growing group of dimeric proteins. TGF beta and several other members of this superfamily are known to play an important role in wound healing. However, expression of activin dur ing wound healing has not been demonstrated so far. In this study we h ave analyzed the expression pattern of activin and activin receptors i n normal and wounded skin. We found a large induction of activin A and a minor induction of activin B mRNA expression 1 day after skin injur y and high expression levels of activin A and B were found within the first 7 days after wounding. At 13 days after injury, expression of ac tivin A mRNA had returned to the basal level, whereas high levels of a ctivin B persisted. In situ hybridization studies revealed expression of activin A in the granulation tissue below the wound and activin B i n the hyperproliferative epithelium at the wound edge and in the migra ting epithelial tongue. All known types of activin receptors as well a s the activin binding protein follistatin were expressed in normal and wounded skin. However, no significant induction of receptor gene expr ession was seen during the repair process. The distribution of activin s and activin receptors in the wound suggests multiple autocrine and p aracrine activities of the ligands during wound healing. Our data prov ide evidence for a novel function of activin and indicate that-besides TGF beta s themselves-other members of this superfamily might also pl ay an important role in tissue repair. (C) 1996 Academic Press, Inc.