EFFECT OF TGF-BETA-1 ON REEPITHILIALIZATION OF HUMAN KERATINOCYTES IN-VITRO - AN ORGANOTYPIC MODEL

Transforming growth factor beta-1 (TGF-beta 1) has been shown to inhib it keratinocyte proliferation in vitro yet to stimulate wound healing in vivo. To explore this apparent paradox, the effect of TGF-beta 1 on proliferation and migration was investigated in organotypic cultures after incisional wounding. Organotypic cultures provide a more in vivo - like epidermal tissue and may therefore respond in a different mann er than previous culture models in which epidermal differentiation is incomplete. Without TGF-beta 1, keratinocytes were hyperproliferative in response to wounding. At doses of 2.5 ng/ml or greater, a delay in re-epithelialization was seen at 24 h post-wounding along with a reduc tion in hyperproliferation. By 48 h, however, re-epithelialization was complete in all cultures treated with TGF-beta 1. In particular, 7 ng /ml TGF-beta 1 inhibited proliferation yet had no effect on re-epithel ialization by 48 h. These studies demonstrate that i) TGF-beta 1 induc ed a delay in re-epithelialization, ii) proliferation of wounded kerat inocytes was not inhibited at 2.5 ng/ml doses of TGF-beta 1, and iii) at 7 ng/ml TGF-beta 1, re-epithelialization was complete by 48 h in sp ite of the profound inhibition of cell proliferation. In the organotyp ic model, TGF-beta 1 appears to alter re-epithelialization.