title: Matrix control of transforming growth factor-β function.
abstract: The cytokine transforming growth factor-beta (TGF-β) has multiple effects in both physiological and pathological conditions. TGF-β is secreted as part of a tripartite complex from which it must be released in order to bind to its receptor. Sequestration of latent TGF-β in the extracellular matrix (ECM) is crucial for proper mobilization of the latent cytokine and its activation. However, contrary to expectation, loss-of-function mutations in genes encoding certain matrix proteins that bind TGF-β yield elevated, rather than decreased, TGF-β levels, posing a 'TGF-β paradox.' In this review, we discuss recent findings concerning the relationship of TGF-β, ECM molecules, and latent TGF-β activation and propose a model to resolve the 'TGF-β paradox.'
authors.affiliation: Departments of Cell Biology and Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. masahito.horiguchi@nyumc.org
authors.forename: Masahito
authors.initials: M
authors.lastname: Horiguchi
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Ota
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Rifkin
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta