Uric acid induced inflammatory responses in endothelial cells via up-regulating(pro)renin receptor
Uric acid induced inflammatory responses in endothelial cells via up-regulating(pro)renin receptor
复制标题
尿酸通过上调肾素原受体诱导内皮细胞炎症反应
DOI：
10.1016/j.biopha.2018.10.129
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发表时间：
2019-01-01
影响因子：
7.5
通讯作者：
Jiang, Yinong
中科院分区：
文献类型：
--
作者：
Yang, Xiaolei;Gu, Jie;Jiang, Yinong
高尿酸血症是血管炎症的重要危险因素，但尿酸(UA)在血管内皮细胞中的潜在作用机制尚不清楚。尿酸可刺激人脐静脉内皮细胞肾素-血管紧张素系统(RAS)的激活。(Pro)肾素受体((P)RR)在血管内皮细胞中广泛表达，并能诱导RAS激活。UA诱导的内皮细胞炎症是否通过上调(P)RR仍不清楚。原代培养的人脐静脉内皮细胞在(P)RR或AT1沉默条件下用UA处理。实时荧光定量聚合酶链式反应和单核细胞黏附实验检测内皮细胞的炎症程度。免疫印迹法或免疫荧光法检测(P)RR蛋白水平。丙磺舒用于阻断尿酸的再吸收。微流控芯片检测单核细胞与血管内皮细胞的黏附。我们发现UA刺激HUVECs后，(P)RR表达上调。UA促进血管炎症，表现为细胞因子上调和单核细胞黏附增强。沉默(P)RR可减轻UA诱导的血管炎症。丙磺舒通过抑制(P)RR上调而抑制UA诱导的HUVECs血管炎症。这一发现通过使用微流控芯片得到了进一步验证。我们的研究结果表明，(P)RR在UA刺激所致的内皮炎症反应中起关键作用。
Hyperuricemia is an important risk factor for vascular inflammation, yet the potential mechanisms of uric acid (UA) in endothelial cells are not well understood. UA has been found to stimulate renin-angiotensin system (RAS) activation in human umbilical vein endothelial cells (HUVECs). (Pro)renin receptor ((P)RR) is widely expressed in endothelial cells and able to induce RAS activation. Whether UA-induced endothelial cell inflammation is via up-regulating (P)RR remained unknown. Primary HUVECs were cultured and treated with UA, under the condition of (P)RR or AT1 silencing. The degree of inflammation in HUVECs was determined by Real-time PCR and monocyte adhesion assay. The protein levels of (P)RR were determined by western blotting or immunofluorescence. Probenecid was used to block UA re-absorption in this study. Adhesion of monocytes to HUVECs was elucidated by microfluidic chip. We found (P)RR is up-regulated in HUVECs following UA stimulation. UA promoted vascular inflammation, which was characterized by up-regulating of cytokines and enhanced monocyte adhesion. Silencing of (P)RR alleviated UA-induced vascular inflammation. Probenecid treatment abolished UA-induced vascular inflammation in HUVECs via suppressing (P)RR up-regulation. This finding was further verified by using microfluidic chip. Our findings indicate that (P)RR plays a critical role in endothelial inflammation in response to UA stimulation.