title: Epidermal repair results from activation of follicular and epidermal progenitor keratinocytes mediated by a growth factor cascade.
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.
authors.affiliation: Centre for Cutaneous Research, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London, United Kingdom. simon.myers@qmul.ac.uk
authors.forename: Simon R
authors.initials: SR
authors.lastname: Myers
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Harshad
authors.initials: H
authors.lastname: Navsaria
mesh_terms: D000293:Adolescent; D000328:Adult; D001768:Blister / Q000503:physiopathology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D004817:Epidermis / Q000502:physiology*; D018859:Hair Follicle / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053583:Interleukin-1beta / Q000378:metabolism; D015603:Keratinocytes / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta