Epidermal repair results from activation of follicular and epidermal progenitor keratinocytes mediated by a growth factor cascade

Wound Repair Regen. 2007 Sep-Oct;15(5):693-701. doi: 10.1111/j.1524-475X.2007.00297.x.

Abstract

Reepithelialization of human suction blister wounds was examined in five normal human volunteers over a period of 14 days postwounding to understand the control of keratinocyte migration, proliferation, and differentiation in acute wound healing in a controlled model. The hypothesis that morphological changes and progenitor activation result from altered cytokines and growth factor expression [in particular interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), transforming growth factor alpha (TGF-alpha), TGF-beta 1, and keratinocyte growth factor] was tested using semiquantitative immunohistochemistry combined with reverse transcriptase-polymerase chain reaction of samples from the blister roof, edge, and base. Parallel changes in keratin expression were examined using a wide range of well-established antibodies to multiple keratins and in situ hybridization for keratin 16 (K16), a marker of the hyperproliferative (mucoregenerative) phenotype. Longitudinal morphological, semiquantitative cytokine and growth factor expression, and histometric histone and cytokeratin profiles suggest three phases to reepithelialization: phase 1, or the acute activation phase, early in the first 24 hours postwounding is characterized by epidermal expression of IL-1beta and IL-6, and dermal expression of TGF-beta1, as basal, upper outer root sheath, and putative interfollicular transit amplifying keratinocytes become committed to mitosis; phase 2, or the early activation phase, late in the second 24 hours postwounding, characterized by epidermal expression of TGF-alpha and IL-6 with concurrent suprabasal K16 expression and migration with continued proliferation, and dermal expression of keratinocyte growth factor and IL-6; and phase 3 or restitution over the following 2 weeks, characterized by the return of normal homeostasis, including bulge activation as evidenced by K19 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blister / physiopathology
  • Cell Movement / physiology
  • Cell Proliferation
  • Epidermis / physiology*
  • Hair Follicle / physiology
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Interleukin-1beta / metabolism
  • Keratinocytes / physiology*
  • Wound Healing / physiology*

Substances

  • Interleukin-1beta