Schmidt Eva-Maria, Kraemer Bjoern F, Borst Oliver, Münzer Patrick, Schönberger Tanja, Schmidt Christine, Leibrock Christina, Towhid Syeda T, Seizer Peter, Kuhl Dietmar, Stournaras Christos, Lindemann Stephan, Gawaz Meinrad, Lang Florian
Department of Physiology, University of Tübingen, Tübingen, Germany.
Cell Physiol Biochem. 2012;30(1):259-68. doi: 10.1159/000339062. Epub 2012 Jun 19.
Recent observations pointed to the ability of platelets to migrate and thus to invade the inflamed vascular wall. Platelet migration could be stimulated by stromal cell-derived factor-1 (SDF-1), an effect dependent on phosphatidylinositide-3-kinase (PI3K) and paralleled by activation and phosphorylation of Wiskott-Aldrich syndrome protein (WASP). Migration is inhibited by vinculin, which is similarly regulated by phosphorylation. PI3K-sensitive kinases include the serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored whether SGK1 modifies WASP and vinculin phosphorylation in murine platelets and participates in the regulation of platelet migration. Platelets were isolated from gene-targeted mice lacking SGK1 (sgk1(-/-)) and from their wild type littermates (sgk1(+/+)). Platelet migration stimulated with SDF-1 was significantly less pronounced in sgk1(-/-)platelets than in sgk1(+/+) platelets. Moreover, SDF-1 significantly induced WASP phosphorylation, an effect again reduced in platelets lacking SGK1. Phosphorylation of vinculin was significantly enhanced in sgk1(-/-)platelets and was significantly reduced following treatment of platelets with Ca(2+) chelator BAPTA. Immunohistochemical analysis of in vivo experiments in intestinal vessels after vascular inflammation revealed that transmigration of platelets into inflamed vessel walls was significantly less pronounced in sgk1(-/-)than in sgk1(+/+) mice. In conclusion, SGK1 is a powerful regulator of platelet migration.
最近的观察结果表明血小板具有迁移能力，因此能够侵入炎症血管壁。基质细胞衍生因子-1（SDF-1）可刺激血小板迁移，这种作用依赖于磷脂酰肌醇-3-激酶（PI3K），同时伴有威斯科特-奥尔德里奇综合征蛋白（WASP）的激活和磷酸化。纽蛋白可抑制迁移，其同样受磷酸化调节。PI3K敏感激酶包括血清和糖皮质激素诱导激酶1（SGK1）。本研究探讨了SGK1是否会改变小鼠血小板中WASP和纽蛋白的磷酸化，并参与血小板迁移的调节。从缺乏SGK1的基因敲除小鼠（sgk1(-/-)）及其野生型同窝小鼠（sgk1(+/+)）中分离血小板。用SDF-1刺激后，sgk1(-/-)血小板的迁移明显不如sgk1(+/+)血小板显著。此外，SDF-1可显著诱导WASP磷酸化，在缺乏SGK1的血小板中这种作用再次减弱。sgk1(-/-)血小板中纽蛋白的磷酸化显著增强，在用钙离子螯合剂BAPTA处理血小板后显著降低。对血管炎症后肠道血管进行的体内实验免疫组织化学分析显示，sgk1(-/-)小鼠中血小板向炎症血管壁的迁移明显不如sgk1(+/+)小鼠显著。总之，SGK1是血小板迁移的有力调节因子。
