Epithelial cells utilize cortical actin/myosin to activate latent TGF-尾 through integrin 伪_v尾₆-dependent physical force

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• 作者：Marilyn M. Giacomini^a ; Mark A. Travis^b ; Makoto Kudo^a ; ^c ; Dean Sheppard^a ; ^{dean.sheppard@ucsf.edu}
• 关键词：Integrin ; 伪v尾6 ; Contraction ; TGF-尾 ; Sphingosine 1-Phosphate
• 刊名：Experimental Cell Research
• 出版年：2012
• 期刊代码：292_00144827
• 类别：med
• 出版时间：1 April, 2012
• 卷：318
• 期：6
• 页码：716-722
• 文件大小：833 K

摘要

Transforming Growth Factor Beta (TGF-尾) 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 伪_v尾₆ activates TGF-尾 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-尾 through a pathway that involves Rho Kinase, non-muscle myosin, the 伪_v尾₆ integrin, and the generation of mechanical tension. Interestingly, lung epithelial cells appear to exert force on latent TGF-尾 using sub-cortical actin/myosin rather than the stress fibers utilized by fibroblasts and other traditionally 鈥渃ontractile鈥?cells. These findings extend recent evidence suggesting TGF-尾 can be activated by integrin-mediated mechanical force and suggest that this mechanism is important for an integrin (伪_v尾₆) and a cell type (epithelial cells) that have important roles in biologically relevant TGF-尾 activation in vivo.