Effect of TGF-beta 1 on re-epithelialization of human keratinocytes in vitro: an organotypic model.
Transforming growth factor beta-1 (TGF-beta 1) has been shown to inhibit keratinocyte proliferation in vitro yet 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-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 reduction 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-epithelialization by 48 h. These studies demonstrate that i) TGF-beta 1 induced a delay in re-epithelialization, ii) proliferation of wounded keratinocytes 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 spite of the profound inhibition of cell proliferation. In the organotypic model, TGF-beta 1 appears to alter re-epithelialization.
Garlick
J A
JA
Department of Oral Biology and Pathology, School of Dental Medicine, State University of New York at Stony Brook 11794-8702.
Taichman
L B
LB
D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014945:Wound Healing / Q000502:physiology
D016212:Transforming Growth Factor beta