Extracellular calcium-sensing receptor is functionally expressed in human artery
Extracellular calcium-sensing receptor is functionally expressed in human artery
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DOI：
10.1152/ajprenal.00474.2006
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发表时间：
2007-09-01
影响因子：
4.2
通讯作者：
Zehnder, Daniel
中科院分区：
文献类型：
--
作者：
Molostvov, Guerman;James, Sean;Zehnder, Daniel
细胞外钙敏感受体在人动脉中功能性表达。美国肾脏生理学杂志293：F946-F955，2007年。首次发表于2007年5月30日; doi：10.1152/ajprenal.00474.2006。-加速中膜钙化是慢性肾脏病（CKD）患者过早心血管死亡的主要原因。有证据表明，细胞外Ca-2（+）浓度和血管平滑肌细胞可能在血管钙化的发病机制中起关键作用。钙敏感受体（CaSR）是一种G蛋白偶联受体，在一系列组织中表达，但其在心血管系统中的表达和功能的表征是有限的。本文报道了人主动脉平滑肌细胞（HAoSMC）中CaSR mRNA（RT-PCR）和蛋白（Western blotting和免疫细胞化学）的表达。用Ca 2（+）（0-5 mM; 0-30 min）或CaSR激动剂庆大霉素和新霉素（0-300 μ M; 0-30 min）处理HAoSMC导致ERK 1/2的剂量和时间依赖性磷酸化。庆大霉素和新霉素介导的ERK 1/2刺激被PD-98059（一种ERK激活激酶1（MEK 1）抑制剂）预处理抑制，证实了所观察到的效应的特异性。HAoSMC中ERK 1/2的激活被抑制，CaSR的表达被特异性小干扰RNA（small interference RNA，small interference RNA，siRNA）敲低，证实了新霉素/庆大霉素诱导的MEK 1/ERK 1/2激活是通过CaSR介导的。CaSR mRNA和蛋白在正常人（肾脏供体）和终末期肾病（ESRD）患者的大动脉和小动脉中也有表达。平滑肌细胞和内皮细胞中检测到CaSR。在ESRD患者的动脉中表达显著较低。总之，这些数据不仅证明了人动脉中存在功能性CaSR，而且还显示了CaSR表达与CKD进展之间的相关性。
Extracellular calcium-sensing receptor is functionally expressed in human artery. Am J Physiol Renal Physiol 293: F946-F955, 2007. First published May 30, 2007; doi:10.1152/ajprenal.00474.2006.- Accelerated medial calcification is a major cause of premature cardiovascular mortality in patients with chronic kidney disease (CKD). Evidence suggests that extracellular concentration of Ca-2 (+) and vascular smooth muscle cells may play a pivotal role in the pathogenesis of vascular calcification. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor that is expressed in a range of tissues, but characterization of its expression and function in the cardiovascular system is limited. Here we report the expression of CaSR mRNA (RT-PCR) and protein ( Western blotting and immunocytochemistry) in human aortic smooth muscle cells (HAoSMC). Treatment of HAoSMC with Ca2 (+) (0-5 mM; 0-30 min) or the CaSR agonists gentamycin and neomycin ( 0-300 mu M; 0-30 min) resulted in a dose- and time-dependent phosphorylation of ERK1/2. Gentamycin- and neomycin-mediated ERK1/2 stimulation was inhibited by pretreatment with PD-98059, an ERK-activating kinase 1 (MEK1) inhibitor, confirming specificity of the observed effects. ERK1/2 activation was inhibited in HAoSMC, with CaSR expression knocked down by transfection with specific small-interference RNA, which confirmed that the observed neomycin/gentamycininduced MEK1/ERK1/2 activation was mediated via the CaSR. CaSR mRNA and protein were also expressed in large and small arteries from normal subjects ( kidney donors) and patients with end-stage renal disease ( ESRD). The CaSR was detected in smooth muscle and endothelial cells. Expression was significantly lower in arteries from ESRD patients. In conclusion, these data not only demonstrate the presence of a functional CaSR in human artery but show a correlation between CaSR expression and progression of CKD.