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 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.
Nishimura
Stephen L
SL
Department of Anatomic Pathology, University of California San Francisco, San Francisco, CA 94143, USA. stephen.nishimura@ucsf.edu
D000818:Animals; D005355:Fibrosis / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007107:Immune System / Q000196:embryology / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D038081:Organogenesis; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016023:Integrins; D016212:Transforming Growth Factor beta