GROUP VIA PHOSPHOLIPASE A2 (IPLA2BETA) IN TRANSCRIPTIONAL UPREGULATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 RGS2(G蛋白信号转导调节因子-2)基因缺陷的小鼠表现出严重的高血压，高血压患者中存在RGS2的遗传变异。血管紧张素II(Ang II)上调血管平滑肌细胞(VSMC)RGS2基因表达是血压稳态的一种潜在的负反馈机制，但其发生机制尚不清楚。在此，我们证明了通过磷脂酶A2的组(iPLA2β)在Ang II诱导的VSMC RGS2 mRNA上调中起关键作用的三种独立途径，包括用溴烯醇内酯自杀底物进行药物抑制，用反义寡核苷酸抑制iPLA2β的表达，以及在iPLA2β缺失的小鼠中进行基因缺失。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rgs2 (regulator of G-protein signaling-2)-deficient mice exhibit severe hypertension, and genetic variations of RGS2 occur in hypertensive patients. RGS2 mRNA up-regulation by angiotensin II (Ang II) in vascular smooth muscle cells (VSMC) is a potentially important negative feedback mechanism in blood pressure homeostasis, but how it occurs is unknown. Here we demonstrate that group VIA phospholipase A2 (iPLA2beta) plays a pivotal role in Ang II-induced RGS2 mRNA up-regulation in VSMC by three independent approaches, including pharmacologic inhibition with a bromoenol lactone suicide substrate, suppression of iPLA2beta expression with antisense oligonucleotides, and genetic deletion in iPLA2beta-null mice.