Protection of transforming growth factor β activity by heparin and fucoidan

Document Type

Journal Article

Publication Date

1-1-1994

Journal

Journal of Cellular Physiology

Volume

159

Issue

1

DOI

10.1002/jcp.1041590108

Abstract

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 α2‐macroglobulin (α2‐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 125I‐TGF‐β1 and activated α2‐M. Electrophoresis of 125I‐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 125I‐TGF‐β1 and doubled the amount of cell‐associated 125I‐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. Copyright © 1994 Wiley‐Liss, Inc.

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