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    Transcription factor p63 regulates key genes and wound repair in human airway epithelial Basal cells

    Access Status
    Fulltext not available
    Authors
    Warner, S.
    Hackett, T.
    Shaheen, F.
    Hallstrand, T.
    Kicic, Anthony
    Stick, S.
    Knight, D.
    Date
    2013
    Type
    Journal Article
    
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    Citation
    Warner, S. and Hackett, T. and Shaheen, F. and Hallstrand, T. and Kicic, A. and Stick, S. and Knight, D. 2013. Transcription factor p63 regulates key genes and wound repair in human airway epithelial Basal cells. American Journal of Respiratory Cell and Molecular Biology. 49 (6): pp. 978-988.
    Source Title
    American Journal of Respiratory Cell and Molecular Biology
    DOI
    10.1165/rcmb.2012-0447OC
    ISSN
    1044-1549
    URI
    http://hdl.handle.net/20.500.11937/63359
    Collection
    • Curtin Research Publications
    Abstract

    The airway epithelium in asthma displays altered repair and incomplete barrier formation. Basal cells are the progenitor cells of the airway epithelium, and can repopulate other cell types after injury. We previously reported increased numbers of basal cells expressing the transcription factor p63 in the airway epithelium of patients with asthma. Herewesoughttodetermine themolecular consequencesof p63 expression in basal human airway epithelial cells during wound repair. Because at least six isoforms of p63 exist (N-terminally truncated [ΔN] versus transcriptional activation promoter variants and α, β, or γ 3' splice variants), the expression of all isoforms was investigatedinprimaryhumanairwayepithelialcells(pHAECs). Wemodulated p63 expression, using small interfering RNA (siRNA) and adenoviral constructs to determine the effects of p63 on 21 candidate target genes by RT-PCR, and on repair using a scratch wound assay. We found that basal pHAECs from asthmatic and nonasthmatic donors predominantly expressed the N-terminally truncated p63α variant (ΔNp63α) isoform, with no disease-specific differences in expression. The knockdown of ΔNp63, using specific siRNA, decreased the expression of 11 out of 21 genes associated with epithelial repair and differentiation, including β-catenin, epidermal growth factor receptor, and Jagged1. The loss of ΔNp63 significantly inhibited wound closure (which was associated with the decreased expression of β-catenin and Jagged1), reduced epithelial proliferation as measured by Ki-67 staining, and increased E-cadherin expression, potentially preventing cytokinesis. In conclusion, ΔNp63α is the major isoform expressed in basal pHAECs, and is essential for epithelial wound repair. The role of ΔNp63α in epithelial barrier integrity requires further study to understand its role in health and disease. Copyright © 2013 by the American Thoracic Society.

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