PROTECTION OF TRANSFORMING GROWTH-FACTOR-BETA-1 ACTIVITY BY HEPARIN AND FUCOIDAN
PROTECTION OF TRANSFORMING GROWTH-FACTOR-BETA-1 ACTIVITY BY HEPARIN AND FUCOIDAN
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DOI：
10.1002/jcp.1041590108
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发表时间：
1994-04-01
影响因子：
5.6
通讯作者：
BORTH, W
中科院分区：
文献类型：
--
作者：
MCCAFFREY, TA;FALCONE, DJ;BORTH, W
转化生长因子- β (tgf - β)蛋白家族在增殖、分化和细胞外基质合成方面发挥着多种有效的作用。然而，对于内源性tgf - β活性在体外或体内的稳定性或加工过程，我们所知相对较少。我们之前的研究表明：1)tgf - β 1具有较强的肝素结合特性，这是由于碘化而未被认识到的；2)肝素和某些其他多阴离子可以阻断tgf - β 1与α 2-巨球蛋白（α 2-m）的结合。本研究探讨了肝素样分子对细胞周围环境中tgf - β 1信号稳定性的影响。结果表明，肝素和岩藻糖聚糖（一种天然存在的硫酸化L聚焦聚合物）抑制了i -125- tgf - β 1与活化的α 2- m之间初始非共价相互作用的形成。I-125-TGF-beta1的电泳显示褐藻糖聚糖保护TGF-beta1免受纤溶酶和胰蛋白酶的蛋白水解降解。虽然纤溶蛋白很少（如果有的话）激活来自血管平滑肌细胞（SMC）的潜伏tgf - β，但纤溶蛋白降解酸激活的tgf - β和纯化的tgf - β，并且这种降解被岩藻聚糖抑制。在体外，肝素和岩藻聚糖使i -125- β - a1的半衰期增加了两倍，使细胞相关的i -125- tgf - β - a1的数量增加了一倍。与这种保护作用一致的是，肝素和岩藻胶处理的SMC显示出活性tgf - β活性水平升高，而不是潜在的tgf - β活性。(C) 1994 Wiley-Liss, Inc。
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-beta1 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-beta1 to alpha2-macroglobulin (alpha2-M). The present studies investigated the influence of heparin-like molecules on the stability of the TGF-beta1 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 I-125-TGF-beta1 and activated alpha2-M. Electrophoresis of I-125-TGF-beta1 showed that fucoidan protects TGF-beta1 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-beta1, and this degradation was inhibited by fucoidan. In vitro, heparin and fucoidan tripled the half-life of I-125-beta1 and doubled the amount of cell-associated I-125-TGF-beta1. Consistent with this protective effect, heparin- and fucoidan-treated SMC demonstrated elevated levels of active, but not latent, TGF-beta activity. (C) 1994 Wiley-Liss, Inc.