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Am J Pathol. 2009 Oct;175(4):1362-70. doi: 10.2353/ajpath.2009.090393. Epub 2009 Sep 3.

Integrin-mediated transforming growth factor-beta activation, a potential therapeutic target in fibrogenic disorders.

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  • 1Department of Anatomic Pathology, University of California San Francisco, San Francisco, CA 94143, USA.


A subset of integrins function as cell surface receptors for the profibrotic cytokine transforming growth factor-beta (TGF-beta). TGF-beta is expressed in an inactive or latent form, and activation of TGF-beta is a major mechanism that regulates TGF-beta function. Indeed, important TGF-beta activation mechanisms involve several of the TGF-beta binding integrins. Knockout mice suggest essential roles for integrin-mediated TGF-beta activation in vessel and craniofacial morphogenesis during development and in immune homeostasis and the fibrotic wound healing response in the adult. Amplification of integrin-mediated TGF-beta activation in fibrotic disorders and data from preclinical models suggest that integrins may therefore represent novel targets for antifibrotic therapies.

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