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Protection of transforming growth factor β activity by heparin and fucoidan
Author(s) -
McCaffrey Timothy A.,
Falcone Domenick J.,
Vicente Diane,
Du Baoheng,
Consigli Seth,
Borth Wolfgang
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041590108
Subject(s) - fucoidan , plasmin , heparin , transforming growth factor , biochemistry , extracellular matrix , chemistry , in vitro , fucose , sulfation , growth factor , microbiology and biotechnology , biology , polysaccharide , receptor , enzyme , glycoprotein
The transforming growth factor‐β (TGF‐β) 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‐β activity in vitro or in vivo. Our previous work indicated that (1) TGF‐β1 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‐β1 to α 2 ‐macroglobulin (α 2 ‐M). The present studies investigated the influence of heparin‐like molecules on the stability of the TGF‐β1 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 125 I‐TGF‐β1 and activated α 2 ‐M. Electrophoresis of 125 I‐TGF‐β1 showed that fucoidan protects TGF‐β1 from proteolytic degradation by plasmin and trypsin. While plasmin caused little, if any, activation of latent TGF‐β derived from vascular smooth muscle cells (SMC), plasmin degraded acid‐activated TGF‐β, and purified TGF‐β1, and this degradation was inhibited by fucoidan. In vitro, heparin and fucoidan tripled the half‐life of 125 I‐TGF‐β1 and doubled the amount of cell‐associated 125 I‐TGF‐β1. Consistent with this protective effect, heparin‐ and fucoidan‐treated SMC demonstrated elevated levels of active, but not latent, TGF‐β activity. © 1994 wiley‐Liss, Inc.