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Circulation:GPRC5B在血管平滑肌细胞收缩和分化中的调控作用

2020-05-01 QQY MedSci原创

G蛋白偶联受体是血管平滑肌细胞(SMCs)收缩和分化的重要调节剂,但是SMC表达的孤儿G蛋白偶联C类受体5组B成员(GPRC5B)的具体功能尚不清楚。

G蛋白偶联受体是血管平滑肌细胞(SMCs)收缩和分化的重要调节剂,但是SMC表达的孤儿G蛋白偶联C类受体5组B成员(GPRC5B)的具体功能尚不清楚。

本研究在体外研究了GPRC5B在人、小鼠SMCs收缩性和去分化的调节作用,在体内研究了在动脉高血压和动脉粥样硬化条件下,iSM-Gprc5b-KO(他莫昔芬诱导的,SMC特异性敲除)小鼠SMCs的收缩性和去分化作用。

SMC特异性Gprc5b-KOs小鼠来源的肠系膜动脉离体后的前列环素受体(IP)依赖性的松弛显著增强,而对其他放松或收缩刺激因素的反应是正常的。在体外,敲除人主动脉SMC的GPRC5B可导致IP依赖性cAMP产生增加,并持续促进SMC松弛。与此IP介导的放松促进作用相一致,iSM-Gprc5b-KO小鼠受到了动脉高压保护,而IP拮抗剂可抵消这种保护作用。

在机制上,研究人员证明无论是在体内还是体外,敲低GPRC5B都可增加IP的膜定位;是GPRC5B与IP发生物理性的相互作用,而非其他G蛋白偶联受体。最后,研究人员发现在GPRC5B缺陷的SMCs中增强IP信号不仅可促进松弛作用,还可预防动脉粥样硬化发生过程中的去分化,从而减少斑块负荷,并增加纤维帽中的SMC分化。

总而言之,本研究表明GPRC5B可通过负面调节IP信号传导来调节血管SMC收缩和分化

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    2020-05-01 1902498648_44512810

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