Role of hepsin in factor VII activation in zebrafish
Role of hepsin in factor VII activation in zebrafish
复制标题
DOI：
10.1016/j.bcmd.2013.07.014
复制
发表时间：
2014-01-01
影响因子：
2.3
通讯作者：
Jagadeeswaran, Pudur
中科院分区：
文献类型：
--
作者：
Khandekar, Gauri;Jagadeeswaran, Pudur
因子VII是外源性凝血级联反应的引发剂，主要以其酶原形式（因子VII）和少量以其活化形式（因子Vila）在人血浆中循环。然而，尽管使用目前可用的模型系统进行了深入的研究，但Vila因子初始生成的机制尚不清楚。早期的研究表明丝氨酸蛋白酶、因子VII激活蛋白酶和hepsin在激活因子VII中起作用，但仍存在争议。本文首次测定了斑马鱼成年群体中凝血因子Vila和凝血因子VII的水平，并以斑马鱼为模型系统，重新评价了这两种丝氨酸蛋白酶在激活凝血因子VII中的作用。进行因子VII活化蛋白酶和hepsin的敲低，然后测定它们对因子Vila浓度和外源性凝血的影响，如通过动力学凝血酶原时间测量的。因子VII活化蛋白酶敲低显示动力学凝血酶原时间没有变化，对因子Vila水平没有影响，而hepsin敲低增加了动力学凝血酶原时间，并显著降低了因子Vila血浆水平。因此，我们的研究结果表明，hepsin在斑马鱼凝血因子VII激活和止血中起着重要的生理作用。(C)2013 Elsevier Inc. All rights reserved.
Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor Vila. However, the mechanism of initial generation of factor Vila is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor Vila and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor Vila concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor Vila levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor Vila plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish. (C) 2013 Elsevier Inc. All rights reserved.