Bertrand Y, Demeule M, Rivard G-E, Béliveau R
Laboratoire de Médecine Moléculaire, Service d'Hématologie-Oncologie, Hôpital Ste-Justine-UQAM, C.P. 8888, Succursale Centre-ville, Montréal, Québec, Canada H3C 3P8.
Biochim Biophys Acta. 2006 Oct;1763(10):1024-30. doi: 10.1016/j.bbamcr.2006.08.006. Epub 2006 Aug 11.
Tissue-type plasminogen activator (tPA) and its substrate plasminogen (Plg) are key components in the fibrinolytic system. We have recently demonstrated, that truncated human recombinant soluble melanotransferrin (sMTf) could stimulate the activation of Plg by urokinase plasminogen activator and inhibit angiogenesis. Since various angiogenesis inhibitors were shown to stimulate tPA-mediated plasminogen activation, we examined the effects of sMTf on tPA-dependent fibrinolysis. This study demonstrated that sMTf enhanced tPA-activation of Plg by 6-fold. sMTf also increased the release of [125I]-fibrin fragments by tPA-activated plasmin. Moreover, we observed that the interaction of sMTf with Plg provoked a change in the fibrin clot structure by cleaving the fibrin alpha and beta chains. Overall, the present study shows that sMTf modulates tPA-dependent fibrinolysis by modifying the clot structure. These results also suggest that sMTf properties could involve enhanced dissolution of the provisional extracellular fibrin matrix.
组织型纤溶酶原激活剂（tPA）及其底物纤溶酶原（Plg）是纤维蛋白溶解系统的关键组成部分。我们最近证明，截短的人重组可溶性黑素转铁蛋白（sMTf）可刺激尿激酶型纤溶酶原激活剂对Plg的激活，并抑制血管生成。由于各种血管生成抑制剂已被证明可刺激tPA介导的纤溶酶原激活，我们研究了sMTf对tPA依赖性纤维蛋白溶解的影响。本研究表明，sMTf使Plg的tPA激活增强了6倍。sMTf还增加了tPA激活的纤溶酶释放的[125I] - 纤维蛋白片段。此外，我们观察到sMTf与Plg的相互作用通过切割纤维蛋白α链和β链引发了纤维蛋白凝块结构的变化。总体而言，本研究表明sMTf通过改变凝块结构来调节tPA依赖性纤维蛋白溶解。这些结果还表明，sMTf的特性可能涉及临时细胞外纤维蛋白基质溶解的增强。
