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

MM Giacomini, MA Travis, M Kudo… - Experimental cell research, 2012 - Elsevier
MM Giacomini, MA Travis, M Kudo, D Sheppard
Experimental cell research, 2012Elsevier
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 …
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.
Elsevier