Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts
Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts
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DOI：
10.1210/en.2003-0128
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发表时间：
2003-06-01
期刊：
影响因子：
4.8
通讯作者：
Kangawa, K
中科院分区：
文献类型：
--
作者：
Horio, T;Tokudome, T;Kangawa, K
c型利钠肽（C-type natriuretic peptide， CNP）是利钠肽家族的第三个成员，与心房利钠肽和脑利钠肽不同，主要在中枢神经系统和血管内皮细胞中合成。然而，目前还没有关于培养心肌细胞产生CNP的研究。在这里，我们研究了CNP在培养的心室细胞中的产生和局部作用。在无血清条件下，成年大鼠心脏成纤维细胞分泌免疫反应性CNP具有时间依赖性。tgf - β 1、碱性成纤维细胞生长因子和内皮素-1显著刺激CNP的分泌。Northern blot检测到CNP及其特异性受体（guanyyl cyclase-B） mRNA在心脏成纤维细胞中显著表达。CNP比心房肽和脑钠肽更强烈地刺激成纤维细胞内cGMP的产生。CNP对心肌成纤维细胞的DNA和胶原合成均有抑制作用，且其抑制作用强于心房和脑利钠肽。CNP对DNA和胶原合成的抑制作用通过cGMP类似物8-溴cGMP重现。目前的研究结果表明，CNP是在心脏成纤维细胞中合成和分泌的，并表明CNP对成纤维细胞增殖和细胞外基质的产生有抑制作用，可能是通过guanyyl环化酶b介导的cgmp依赖过程。由心脏成纤维细胞产生的CNP可能作为一种自分泌调节因子，对过度的心脏纤维化起作用。
C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is known to be synthesized in the central nervous system and vascular endothelial cells, in contrast to atrial natriuretic peptide and brain natriuretic peptide. However, there have been no studies concerning CNP production in cultured cardiac cells. Here, we examined the production and the local effect of CNP in cultured ventricular cells. Under serum-free conditions, adult rat cardiac fibroblasts secreted immunoreactive CNP time dependently. TGF-beta1, basic fibroblast growth factor, and endothelin-1 significantly stimulated CNP secretion. Northern blot analysis detected significant expressions of CNP and its specific receptor (guanylyl cyclase-B) mRNA in cardiac fibroblasts. CNP stimulated intracellular cGMP production in fibroblasts more intensely than atrial and brain natriuretic peptides. CNP inhibited both DNA and collagen syntheses of cardiac fibroblasts, and these inhibitory effects by CNP were stronger than by atrial and brain natriuretic peptides. The inhibition by CNP of DNA and collagen syntheses was reproduced by a cGMP analog, 8-bromo cGMP. The present findings demonstrate that CNP is synthesized in and secreted from cardiac fibroblasts and suggest that CNP has a suppressive effect on fibroblast proliferation and extracellular matrix production, probably via the guanylyl cyclase-B-mediated cGMP-dependent process. CNP produced by cardiac fibroblasts may play a role as an autocrine regulator against excessive cardiac fibrosis.