Transforming growth factor beta-1 (TGF-β1) has been shown to inhibit keratinocyte proliferation in vitro yet to stimulate wound healing in vivo. To explore this apparent paradox, the effect of TGF-β1 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 manner than previous culture models in which epidermal differentiation is incomplete.

Without TGF-β1, 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 reduction in hyperproliferation. By 48 h, however, re-epithelialization was complete in all cultures treated with TGF-β1. In particular, 7 ng/ml TGF-β1 inhibited proliferation yet had no effect on re-epithelialization by 48 h. These studies demonstrate that i) TGF-β1 induced a delay in re-epithelialization, ii) proliferation of wounded keratinocytes was not inhibited at 2.5 ng/ml doses of TGF-β1, and iii) at 7 ng/ml TGF-β1, re-epithelialization was complete by 48 h in spite of the profound inhibition of cell proliferation. In the organotypic model, TGF-β1 appears to alter re-epithelialization.