Effect of TGF-beta 1 on re-epithelialization of human keratinocytes in vitro: an organotypic model

J Invest Dermatol. 1994 Oct;103(4):554-9. doi: 10.1111/1523-1747.ep12396847.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division / drug effects
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Models, Biological
  • Transforming Growth Factor beta / pharmacology*
  • Wound Healing / physiology


  • Transforming Growth Factor beta