OBJECTIVE HuR (human antigen R)-an RNA-binding protein-is involved in regulating mRNA stability by binding adenylate-uridylate-rich elements. This study explores the role of HuR in the regulation of smooth muscle contraction and blood pressure. Approach and Results: Vascular HuRSMKO (smooth muscle-specific HuR knockout) mice were generated by crossbreeding HuRflox/flox mice with α-SMA (α-smooth muscle actin)-Cre mice. As compared with CTR (control) mice, HuRSMKO mice showed hypertension and cardiac hypertrophy. HuR levels were decreased in aortas from hypertensive patients and SHRs (spontaneously hypertensive rats), and overexpression of HuR could lower the blood pressure of SHRs. Contractile response to vasoconstrictors was increased in mesenteric artery segments isolated from HuRSMKO mice. The functional abnormalities in HuRSMKO mice were attributed to decreased mRNA and protein levels of RGS (regulator of G-protein signaling) protein(s) RGS2, RGS4, and RGS5, which resulted in increased intracellular calcium increase. Consistently, the degree of intracellular calcium ion increase in HuR-deficient smooth muscle cells was reduced by overexpression of RGS2, RGS4, or RGS5. Finally, administration of RGS2 and RGS5 reversed the elevated blood pressure in HuRSMKO mice. CONCLUSIONS Our findings indicate that HuR regulates vascular smooth muscle contraction and maintains blood pressure by modulating RGS expression.

中文翻译：

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HuR（人类抗原R）调节血管平滑肌的收缩并维持血压。

目的HuR（人类抗原R）-一种RNA结合蛋白，通过结合富含腺苷酸-尿苷酸的元素参与调节mRNA的稳定性。这项研究探讨了HuR在调节平滑肌收缩和血压中的作用。方法和结果：通过将HuRflox / flox小鼠与α-SMA（α平滑肌肌动蛋白）-Cre小鼠杂交来产生血管HuRSMKO（平滑肌特异性HuR基因敲除）小鼠。与CTR（对照）小鼠相比，HuRSMKO小鼠表现出高血压和心脏肥大。高血压患者和SHR（自发性高血压大鼠）的主动脉中HuR水平降低，HuR的过表达可降低SHR的血压。从HuRSMKO小鼠分离的肠系膜动脉节段中，对血管收缩剂的收缩反应增加。HuRSMKO小鼠的功能异常归因于RGS（G蛋白信号调节剂）蛋白RGS2，RGS4和RGS5的mRNA和蛋白水平降低，这导致细胞内钙增加增加。一致地，RGS2，RGS4或RGS5的过表达降低了HuR缺失的平滑肌细胞中细胞内钙离子增加的程度。最后，施用RGS2和RGS5可逆转HuRSMKO小鼠的血压升高。结论我们的发现表明，HuR通过调节RGS表达来调节血管平滑肌收缩并维持血压。RGS2，RGS4或RGS5的过表达降低了HuR缺失的平滑肌细胞中细胞内钙离子增加的程度。最后，施用RGS2和RGS5可逆转HuRSMKO小鼠的血压升高。结论我们的发现表明，HuR通过调节RGS表达来调节血管平滑肌收缩并维持血压。RGS2，RGS4或RGS5的过表达降低了HuR缺失的平滑肌细胞中细胞内钙离子增加的程度。最后，施用RGS2和RGS5可逆转HuRSMKO小鼠的血压升高。结论我们的发现表明，HuR通过调节RGS表达来调节血管平滑肌收缩并维持血压。