Cizmeci-Smith G, Carey D J
Henry Hood MD Research Program, Sigfried, Pa., USA.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2609-16. doi: 10.1161/01.atv.17.11.2609.
Vascular smooth muscle (VSM) cells express transmembrane proteoglycans of the syndecan gene family. We reported previously that the expression of syndecans by VSM cells is regulated by mitogens such as serum, platelet-derived growth factor, and basic fibroblast growth factor and that syndecan expression is induced after balloon injury in vivo. We now show that thrombin is a potent inducer of syndecan-1 expression in VSM cells. Transient transfection experiments with a rat syndecan-1 promoter construct demonstrated that thrombin stimulates transcription of the syndecan-1 gene. Syndecan expression in response to thrombin was not inhibited by downregulation of protein kinase C. Thrombin-induced syndecan-1 expression was dependent on tyrosine kinase activity. Calcium was necessary for syndecan-1 expression, but increasing the intracellular calcium levels was not sufficient to induce syndecan-1 expression. Analysis of antithrombin III (AT III) binding activity revealed that thrombin caused an increase in the synthesis of syndecan-1 molecules that exhibited high-affinity AT III binding. These results suggest that VSM cells could play an important role in controlling local thrombus formation subsequent to vascular injury, via a feedback mechanism that involves thrombin-induced stimulation of an inhibitor of thrombin activity.
血管平滑肌（VSM）细胞表达syndecan基因家族的跨膜蛋白聚糖。我们先前报道，VSM细胞中syndecan的表达受血清、血小板衍生生长因子和碱性成纤维细胞生长因子等促有丝分裂原的调节，并且在体内球囊损伤后syndecan表达被诱导。我们现在表明，凝血酶是VSM细胞中syndecan-1表达的有效诱导剂。用大鼠syndecan-1启动子构建体进行的瞬时转染实验表明，凝血酶刺激syndecan-1基因的转录。蛋白激酶C的下调并未抑制凝血酶诱导的syndecan表达。凝血酶诱导的syndecan-1表达依赖于酪氨酸激酶活性。钙对于syndecan-1表达是必需的，但增加细胞内钙水平不足以诱导syndecan-1表达。抗凝血酶III（AT III）结合活性分析表明，凝血酶导致具有高亲和力AT III结合的syndecan-1分子合成增加。这些结果表明，VSM细胞可能通过涉及凝血酶诱导刺激凝血酶活性抑制剂的反馈机制，在控制血管损伤后局部血栓形成中发挥重要作用。
