Inhibition of VEGF blocks TGF-β 1 production through a PI3K/Akt signalling pathway

K. S. Lee, S. J. Park, S. R. Kim, K. H. Min, K. Y. Lee, Y. H. Choe, S. H. Hong, Y. R. Lee, J. S. Kim, S. J. Hong, Y. C. Lee

    Research output: Contribution to journalArticlepeer-review

    67 Citations (Scopus)

    Abstract

    Vascular endothelial growth factor (VEGF) is a mediator of airway inflammation and remodelling in asthma. Transforming growth factor (TGF)-β 1 plays pivotal roles in diverse biological processes, including tissue remodelling and repair in a number of chronic lung diseases. However, there are few studies elucidating the interactions between VEGF and TGF-β 1 in allergic airway disease. A murine model of allergic airway disease was used to define the mechanism by which VEGF induces subepithelial fibrosis and to investigate a potential relationship between VEGF and TGF-β 1 and the mechanisms by which VEGF signalling regulates TGF-β 1 expression in allergic airway disease. The ovalbumin (OVA)-inhaled murine model revealed the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased peribronchial fibrosis, and increased levels of VEGF and TGF-β 1. Administration of VEGF inhibitors reduced the pathophysiological signs of allergic airway disease and decreased the increased TGF-β 1 levels and peribronchial fibrosis, including phosphoinositide 3-kinase (PI3K) activity after OVA inhalation. In addition, the increased TGF-β 1 levels and collagen deposition after OVA inhalation were decreased by administration of PI3K inhibitors. These results suggest that inhibition of vascular endothelial growth factor attenuates peribronchial fibrosis, at least when mediated by regulation of transforming growth factor-β 1 expression through phosphoinositide 3-kinase/Akt pathway in a murine model of allergic airway disease. Copyright

    Original languageEnglish
    Pages (from-to)523-531
    Number of pages9
    JournalEuropean Respiratory Journal
    Volume31
    Issue number3
    DOIs
    Publication statusPublished - 2008 Mar

    Keywords

    • Airway remodelling
    • Phosphoinositide 3-kinase
    • Subepithelial fibrosis
    • Transforming growth factor-β
    • Vascular endothelial growth factor

    ASJC Scopus subject areas

    • Pulmonary and Respiratory Medicine

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