The anticoagulant factor, protein S, is produced by cultured human vascular smooth muscle cells and its expression is up-regulated by thrombin
The anticoagulant factor, protein S, is produced by cultured human vascular smooth muscle cells and its expression is up-regulated by thrombin
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DOI：
10.1182/blood.v95.6.2008
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发表时间：
2000-03-15
期刊：
影响因子：
20.3
通讯作者：
Kanthou, C
中科院分区：
文献类型：
--
作者：
Benzakour, O;Kanthou, C
抗凝血因子蛋白S是一种分泌的维生素K依赖性γ-羧基化蛋白，主要在肝脏中产生。蛋白S与生长停滞特异性蛋白Gas 6同源，Gas 6的表达在血清撤除后在培养的成纤维细胞中上调。本文报道了体外培养的人血管平滑肌细胞（HVSMCs）合成和分泌蛋白S的情况。Western blot分析表明，培养的HVSMCs和生长停滞的HVSMCs分泌的蛋白S量相近，HVSMCs来源的蛋白S经柠檬酸钡沉淀后被γ-羧基化，具有蛋白C辅因子活性。用维生素K拮抗剂华法林治疗导致细胞内羧基化不足的蛋白S形式的积累，这些蛋白S形式在重新引入维生素K后迅速分泌。北方印迹分析显示培养的HVSMC表达蛋白S转录本。蛋白S信使RNA的表达不受华法林、生长停滞或各种VSMC有丝分裂原如血小板衍生生长因子-BE、碱性成纤维细胞生长因子、转化生长因子-β或肝细胞生长因子的影响。而凝血酶则在mRNA和蛋白质水平上诱导蛋白S的表达上调。我们提供的证据表明，蛋白S分泌培养HVSMCs和它的上调凝血酶，以及早期的报告表明，蛋白S作为这些细胞的促分裂原，表明，除了其已知的作用，在调节血液凝固，蛋白S也可能是一个重要的自分泌因子在血管的病理生理学。(C)2000年，美国血液学会。
The anticoagulant factor protein S is a secreted vitamin K-dependent gamma-carboxylated protein that is mainly made in the liver. Protein S is homologous to the growth arrest specific protein, Gas6, the expression of which is up-regulated in cultured fibroblasts upon serum withdrawal. We report here the synthesis and secretion of protein S by cultured human vascular smooth muscle cells (HVSMCs), Western blot analysis revealed that similar amounts of protein S are secreted by bath growing and growth-arrested HVSMCs, HVSMC-derived protein S was found to be gamma-carboxylated as it was precipitated by barium citrate and was shown to possess protein C cofactor activity. Treatment with the vitamin K antagonist warfarin led to the accumulation of intracellular undercarboxylated protein S forms that were rapidly secreted upon the reintroduction of vitamin K. Northern blotting analysis showed that cultured HVSMCs express a protein S transcript, The expression of protein S messenger RNA was unaffected by either warfarin, growth arrest, or various VSMC mitogens, such as platelet-derived growth factor-BE, basic fibroblast growth factor, transforming growth factor-beta, or hepatocyte growth factor. Thrombin, however, Induced an up-regulation of protein S expression at both messenger RNA and protein levels. The evidence we provide for protein S secretion by cultured HVSMCs and its up-regulation by thrombin, together with earlier reports showing that protein S acts as a mitogen for these cells, suggests that, In addition to its known role in regulating blood clotting, protein S may also be an Important autocrine factor in the pathophysiology of the vasculature. (C) 2000 by The American Society of Hematology.