C type natriuretic peptide down-regulates expression of its cognate receptor in rat aortic smooth muscle cells
C type natriuretic peptide down-regulates expression of its cognate receptor in rat aortic smooth muscle cells
复制标题
DOI：
10.1210/en.2005-0262
复制
发表时间：
2005-11-01
期刊：
影响因子：
4.8
通讯作者：
Gardner, DG
中科院分区：
文献类型：
--
作者：
Rahmutula, D;Gardner, DG
C型利钠（CNP）肽通过血管平滑肌细胞中的B型利钠肽受体（NPR-B）发出信号，以激活该受体固有的颗粒鸟苷酸环化酶活性并升高细胞环GMP水平。在本研究中，我们证明CNP下调该受体的表达，导致NPR-B活性降低。用CNP预处理大鼠主动脉平滑肌细胞可降低NPR-B活性、NPR-B蛋白水平、NPR 2（NPR-B基因）mRNA水平和NPR 2启动子活性。NPR 2启动子活性的降低依赖于相对于转录起始位点在-441和-134之间存在的DNA序列。NPR 2基因表达的减少似乎是通过产生环GMP而起作用的。8-溴环GMP，膜渗透性环GMP类似物，降低NPR 2 mRNA水平和NPR 2启动子活性。心房利钠肽通过A型利钠肽受体（NPR-A）发出信号以增加这些细胞中的环GMP水平，也降低了NPR-B mRNA水平并抑制了NPR-B启动子活性;然而，这种抑制作用与CNP产生的抑制作用不加和，这意味着两种配体通过共同的信号转导途径运输。本报告首次证明CNP能够自动调节其同源受体的表达。
The C-type natriuretic (CNP) peptide signals through the type B natriuretic peptide receptor (NPR-B) in vascular smooth muscle cells to activate the particulate guanylyl cyclase activity intrinsic to that receptor and raise cellular cyclic GMP levels. In the present study, we demonstrate that CNP down-regulates the expression of this receptor leading to a reduction in NPR-B activity. Pretreatment of rat aortic smooth muscle cells with CNP reduces NPR-B activity, NPR-B protein levels, NPR2 (NPR-B gene) mRNA levels, and NPR2 promoter activity. The decrease in NPR2 promoter activity is dependent on DNA sequence present between -441 and -134 relative to the transcription start site. The reduction in NPR2 gene expression appears to operate through generation of cyclic GMP. 8-Bromo cyclic GMP, a membrane-permeable cyclic GMP analog, reduced NPR2 mRNA levels and NPR2 promoter activity. Atrial natriuretic peptide, which signals through the type A natriuretic peptide receptor (NPR-A) to increase cyclic GMP levels in these cells, also reduced NPR-B mRNA levels and inhibited NPR-B promoter activity; however, this inhibition was not additive with that produced by CNP, implying that the two ligands traffic over a common signal transduction pathway. This report provides the first documentation that CNP is capable of autoregulating the expression of its cognate receptor.