Epithelial cells utilize cortical actin/myosin to activate latent TGF-β through integrin αvβ6-dependent physical force

• Published in: Experimental cell research Vol. 318; no. 6; pp. 716 - 722
• Main Authors: Giacomini, Marilyn M., Travis, Mark A., Kudo, Makoto, Sheppard, Dean
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2012
• Subjects: Contraction; Integrin; Sphingosine 1-Phosphate; TGF-β; αvβ6; TGF-β; Integrin; Sphingosine 1-Phosphate; αvβ6; Contraction
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2012.01.020

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 αvβ6 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 αvβ6 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 (αvβ6) and a cell type (epithelial cells) that have important roles in biologically relevant TGF-β activation in vivo. ►S1P induces αvβ6-mediated TGF-β activation through Rho Kinase. ►Cell contraction regulates S1P and LPA induced αvβ6-mediated TGF-β activation. ►S1P and LPA induced αvβ6-mediated TGF-β activation requires cellular tension. ►Increased tension in epithelial cells results from cortical actin.