Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Dysregulated repair in asthmatic paediatric airway epithelial cells: The role of plasminogen activator inhibitor-1

    Access Status
    Fulltext not available
    Authors
    Stevens, P.T.
    Kicic, Anthony
    Sutanto, E.N.
    Knight, D.A.
    Stick, S.M.
    Date
    2008
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Stevens, P.T. and Kicic, A. and Sutanto, E.N. and Knight, D.A. and Stick, S.M. 2008. Dysregulated repair in asthmatic paediatric airway epithelial cells: The role of plasminogen activator inhibitor-1. Clinical and Experimental Allergy. 38 (12): pp. 1901-1910.
    Source Title
    Clinical and Experimental Allergy
    DOI
    10.1111/j.1365-2222.2008.03093.x
    ISSN
    0954-7894
    Faculty
    Faculty of Health Sciences
    School
    School of Public Health
    URI
    http://hdl.handle.net/20.500.11937/76823
    Collection
    • Curtin Research Publications
    Abstract

    Background: Asthma is associated with structural changes to airways such as extracellular matrix deposition and epithelial damage. Evidence suggests that asthmatic airway epithelial repair is abnormal and that elevated plasminogen activator inhibitor-1 levels observed in asthma may be involved in the epithelial repair process and in excessive matrix accumulation. Objective: To assess the ability of asthmatic airway epithelial cells (AECs) to repair mechanically induced wounds and to investigate the role that plasminogen activator inhibitor-1 plays in the repair process. Methods: AECs were isolated from atopic asthmatic and healthy non-atopic children by bronchial brushing, subcultured and wound repair experiments were performed. Plasminogen activator inhibitor-1 gene expression was assessed using real-time PCR while protein activity was measured in cell lysates as well as plasma. The role of plasminogen activator inhibitor-1 in epithelial proliferation and wound repair was investigated using siRNA. Results: Cells from asthmatic children have a significantly longer repair time in comparison with cells from otherwise healthy donors. Plasminogen activator inhibitor-1 mRNA expression was up-regulated 68-fold in freshly isolated asthmatic cells compared with normal cells, and protein levels were also significantly elevated in the asthmatic cell lysates, but plasma levels were similar in both groups. Plasminogen activator inhibitor-1 cells expression increased in both cohorts during culture. Gene silencing substantially reduced the rate of proliferation in asthmatic and healthy cells. Mechanical wounding of epithelial monolayers induced plasminogen activator inhibitor-1 expression in asthmatic and non-asthmatic cohorts, while gene silencing delayed wound repair of healthy cell, with minimal effect on those from asthmatics. Conclusion: Asthmatic AECs are inherently dysfunctional in their ability to repair wounds; plasminogen activator inhibitor-1 mRNA and protein activity are constitutively up-regulated in asthmatic epithelium and play functional roles in both proliferation and repair of healthy cells. In asthmatic cells, elevated plasminogen activator inhibitors-1 levels fail to stimulate epithelial repair. © 2008 The Authors.

    Related items

    Showing items related by title, author, creator and subject.

    • Reduced transforming growth factor ß1 (TGF-ß1) in the repair of airway epithelial cells of children with asthma
      Ling, K.; Sutanto, E.; Iosifidis, T.; Kicic-Starcevich, E.; Looi, K.; Garratt, L.; Martinovich, K.; Lannigan, F.; Knight, D.; Stick, S.; Kicic, Anthony (2016)
      © 2016 Asian Pacific Society of Respirology Background and objective: Evidence into the role of TGF-ß1 in airway epithelial repair in asthma is still controversial. This study tested the hypothesis that the reduced TGF-ß1 ...
    • Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium
      Kicic, Anthony ; Hallstrand, T.S.; Sutanto, E.N.; Stevens, P.T.; Kobor, M.S.; Taplin, C.; Paré, P.D.; Beyer, R.P.; Stick, S.M.; Knight, D.A. (2010)
      Rationale: Damage to airway epitheliumis followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound ...
    • Transcription factor p63 regulates key genes and wound repair in human airway epithelial Basal cells
      Warner, S.; Hackett, T.; Shaheen, F.; Hallstrand, T.; Kicic, Anthony; Stick, S.; Knight, D. (2013)
      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 ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.