TGF-BETA-1 STIMULATES EXPRESSION OF KERATINOCYTE INTEGRINS DURING REEPITHILIALIZATION OF CUTANEOUS WOUNDS

Epidermal keratinocytes migrate over a provisional matrix during the re-epithelialization of cutaneous wounds. We have investigated the expression of integrins and of transforming growth factor-beta 1 (TGF-beta 1) during re-epithelialization in a porcine model. Tissue specimens were collected at different times after injury and stained with antibodies against subunits of the fibronectin receptor, integrin alpha 5 beta 1, and the vitronectin receptor, integrin alpha v beta 5. Intense staining was observed in the migrating keratinocytes of 5-d wounds; basal and suprabasal cells were stained around the entire cell periphery. Staining returned toward normal levels in 14-d wounds. The appearance of the extracellular form of TGF-beta 1 seemed to be coordinated with the increased expression of integrin subunits: it was detected in migrating keratinocytes and in the adjacent epidermis of early wounds at 5 and 7 d. We also investigated the effect of TGF-beta 1 on cultured epidermal cells. Treating human keratinocytes with TGF-beta 1 increased the levels of mRNA for the integrin subunits alpha 5, alpha v, and beta 5, but had little effect on beta 1. The corresponding cell-surface expression of alpha 5 and alpha v was also increased after treatment. Thus, during wound repair, TGF-beta 1 may induce epidermal keratinocytes to express integrins that facilitate the migratory component of re-epithelialization.