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Epidermal repair results from activation of follicular and epidermal progenitor keratinocytes mediated by a growth factor cascade
Author(s) -
Myers Simon R.,
Leigh Irene M.,
Navsaria Harshad
Publication year - 2007
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2007.00297.x
Subject(s) - epidermal growth factor , progenitor cell , cancer research , progenitor , follicular phase , keratinocyte , microbiology and biotechnology , cascade , medicine , chemistry , biology , stem cell , in vitro , biochemistry , receptor , chromatography
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 β (IL‐1β), interleukin‐6 (IL‐6), transforming growth factor α (TGF‐α), TGF‐β 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‐1β and IL‐6, and dermal expression of TGF‐β1, 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‐α 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.