1 Pharmaceutical Sciences, School of Pharmacy The University of Texas at El Paso TX.
2 Molecular Signal Transduction Section Laboratory of Allergic Diseases NIAID/NIH Bethesda MD.
J Am Heart Assoc. 2019 Mar 5;8(5):e011273. doi: 10.1161/JAHA.118.011273.
Background Members of the regulator of G-protein signaling ( RGS ) family inhibit G-protein coupled receptor signaling by modulating G-protein activity. In platelets, there are 3 different RGS isoforms that are expressed at the protein level, including RGS 16. Recently, we have shown that CXCL 12 regulates platelet function via RGS 16. However, the role of RGS 16 in platelet function and thrombus formation is poorly defined. Methods and Results We used a genetic knockout mouse model approach to examine the role(s) of RGS 16 in platelet activation by using a host of in vitro and in vivo assays. We observed that agonist-induced platelet aggregation, secretion, and integrin activation were much more pronounced in platelets from the RGS 16 knockout ( Rgs16 ) mice relative to their wild type ( Rgs16 ) littermates. Furthermore, the Rgs16 mice had a markedly shortened bleeding time and were more susceptible to vascular injury-associated thrombus formation than the controls. Conclusions These findings support a critical role for RGS 16 in regulating hemostatic and thrombotic functions of platelets in mice. Hence, RGS 16 represents a potential therapeutic target for modulating platelet function.
背景 调节 G 蛋白信号转导的蛋白（RGS）家族成员通过调节 G 蛋白活性来抑制 G 蛋白偶联受体信号转导。在血小板中，有 3 种不同的 RGS 同工型在蛋白质水平上表达，包括 RGS16。最近，我们已经表明，CXCL12 通过 RGS16 调节血小板功能。然而，RGS16 在血小板功能和血栓形成中的作用尚未明确。
方法和结果 我们使用基因敲除小鼠模型方法，通过一系列体外和体内实验，研究了 RGS16 在血小板激活中的作用。我们观察到，与野生型（Rgs16）同窝仔相比，激动剂诱导的血小板聚集、分泌和整合素激活在 RGS16 敲除（Rgs16）小鼠的血小板中更为明显。此外，Rgs16 小鼠的出血时间明显缩短，对血管损伤相关血栓形成的易感性也高于对照组。
结论 这些发现支持 RGS16 在调节小鼠血小板止血和血栓形成功能中的关键作用。因此，RGS16 代表了调节血小板功能的一个潜在治疗靶点。
