Epithelial cells utilize cortical actin/myosin to activate latent TGF-β through integrin α vβ 6-dependent physical force

Marilyn M. Giacomini, Mark A. Travis, Makoto Kudo, Dean Sheppard

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Transforming Growth Factor Beta (TGF-β) is involved in regulating many biological processes and disease states. Cells secrete cytokine as a latent complex that must be activated for it to exert its biological functions. We previously discovered that the epithelial-restricted integrin α vβ 6 activates TGF-β and that this process is important in a number of in vivo models of disease. Here, we show that agonists of G-protein coupled receptors (Sphingosine-1-Phosphate and Lysophosphatidic Acid) which are ligated under conditions of epithelial injury directly stimulate primary airway epithelial cells to activate latent TGF-β through a pathway that involves Rho Kinase, non-muscle myosin, the α vβ 6 integrin, and the generation of mechanical tension. Interestingly, lung epithelial cells appear to exert force on latent TGF-β using sub-cortical actin/myosin rather than the stress fibers utilized by fibroblasts and other traditionally "contractile" cells. These findings extend recent evidence suggesting TGF-β can be activated by integrin-mediated mechanical force and suggest that this mechanism is important for an integrin (α vβ 6) and a cell type (epithelial cells) that have important roles in biologically relevant TGF-β activation in vivo. © 2012 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)716-722
    Number of pages6
    JournalExperimental Cell Research
    Volume318
    Issue number6
    DOIs
    Publication statusPublished - 1 Apr 2012

    Keywords

    • α vβ 6
    • Contraction
    • Integrin
    • Sphingosine 1-Phosphate
    • TGF-β

    Fingerprint

    Dive into the research topics of 'Epithelial cells utilize cortical actin/myosin to activate latent TGF-β through integrin α vβ 6-dependent physical force'. Together they form a unique fingerprint.

    Cite this