Integrin-Mediated Transforming Growth Factor-beta Activation, a Potential Therapeutic Target in Fibrogenic Disorders

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 heating 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. (Am J Pathol 2009, 175:1362-1370; DOI. 10.2353/ajpath.2009.090393)