Journal
JOURNAL OF BIOCHEMISTRY
Volume 152, Issue 4, Pages 321-329Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvs089
Keywords
elastic microfibrils; extracellular matrix; integrin; TGF-beta paradox; transforming growth factor-beta
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Funding
- Banyu Life Science Foundation International
- Uehara Memorial Foundation
- National Cancer Institute [CA034282]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR049698]
- National Marfan Foundation
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The cytokine transforming growth factor-beta (TGF-beta) has multiple effects in both physiological and pathological conditions. TGF-beta 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-beta 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-beta yield elevated, rather than decreased, TGF-beta levels, posing a 'TGF-beta paradox.' In this review, we discuss recent findings concerning the relationship of TGF-beta, ECM molecules, and latent TGF-beta activation and propose a model to resolve the 'TGF-beta paradox.'.
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