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Wound Repair Regen. 2007 Sep-Oct;15(5):693-701.

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

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Centre for Cutaneous Research, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, London, United Kingdom.


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.

[Indexed for MEDLINE]

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