Protection of transforming growth factor-beta 1 activity by heparin and fucoidan.

TitleProtection of transforming growth factor-beta 1 activity by heparin and fucoidan.
Publication TypeJournal Article
Year of Publication1994
AuthorsMcCaffrey TA, Falcone DJ, Vicente D, Du B, Consigli S, Borth W
JournalJ Cell Physiol
Date Published1994 Apr
Keywordsalpha-Macroglobulins, Animals, Anions, Anticoagulants, Cells, Cultured, Fibrinolysin, Heparin, Iodine Radioisotopes, Muscle, Smooth, Vascular, Polysaccharides, Protein Binding, Rats, Rats, Sprague-Dawley, Transforming Growth Factor beta, Trypsin

The transforming growth factor-beta (TGF-beta) family of proteins exert diverse and potent effects on proliferation, differentiation, and extracellular matrix synthesis. However, relatively little is known about the stability or processing of endogenous TGF-beta activity in vitro or in vivo. Our previous work indicated that 1) TGF-beta 1 has strong heparin-binding properties that were not previously recognized because of neutralization by iodination, and 2) heparin, and certain other polyanions, could block the binding of TGF-beta 1 to alpha 2-macroglobulin (alpha 2-M). The present studies investigated the influence of heparin-like molecules on the stability of the TGF-beta 1 signal in the pericellular environment. The results indicate that heparin and fucoidan, a naturally occurring sulfated L-fucose polymer, suppress the formation of an initial non-covalent interaction between 125I-TGF-beta 1 and activated alpha 2-M. Electrophoresis of 125I-TGF-beta 1 showed that fucoidan protects TGF-beta 1 from proteolytic degradation by plasmin and trypsin. While plasmin caused little, if any, activation of latent TGF-beta derived from vascular smooth muscle cells (SMC), plasmin degraded acid-activated TGF-beta, and purified TGF-beta 1, and this degradation was inhibited by fucoidan. In vitro, heparin and fucoidan tripled the half-life of 125I-TGF-beta 1 and doubled the amount of cell-associated 125I-TGF-beta 1. Consistent with this protective effect, heparin- and fucoidan-treated SMC demonstrated elevated levels of active, but not latent, TGF-beta activity.

Alternate JournalJ Cell Physiol
PubMed ID7511146
Grant ListHL01962 / HL / NHLBI NIH HHS / United States
HL18828 / HL / NHLBI NIH HHS / United States
HL42606 / HL / NHLBI NIH HHS / United States
Related Faculty: 
Domenick J. Falcone, Ph.D.

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