Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension.
Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension.
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DOI：
10.1038/ki.2010.257
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发表时间：
2010-10
影响因子：
19.6
通讯作者：
Kurtz, Armin
中科院分区：
文献类型：
--
作者：
Wagner, Charlotte;Jobs, Alexander;Schweda, Frank;Kurtz, Lisa;Kurt, Birguel;Lopez, Maria L. Sequeira;Gomez, R. Ariel;Van Veen, Toon A. B.;De Wit, Cor;Kurtz, Armin
产生肾素的肾小球细胞通过含有连接蛋白40（Cx40）的间隙连接彼此连接并与传入小动脉的内皮细胞连接，这两种细胞类型大量表达Cx40。在这里，我们产生的小鼠与内皮细胞和肾素产生细胞的Cx40的细胞特异性缺失，因为它的全球删除引起局部分离的内皮细胞，肾素分泌过多，高血压的肾素产生细胞。在缺乏内皮细胞Cx40的小鼠中，血压、产生肾素的细胞分布和对肾素分泌的控制与野生型小鼠相似。与此相反，小鼠缺乏Cx40的肾素产生细胞高血压和这些细胞异位定位。虽然这些小鼠的血浆肾素活性和肾脏肾素mRNA水平与对照组没有差异，但在缺乏Cx40的肾脏中，压力对肾素分泌的负调节被逆转为正反馈。因此，我们的研究结果表明，内皮细胞Cx40是不是必不可少的肾素表达和/或释放的控制。Cx40在产生肾素的细胞中对于它们在肾小球区域的正确定位和通过压力控制肾素分泌是必需的。
Renin-producing juxtaglomerular cells are connected to each other and to endothelial cells of afferent arterioles by gap junctions containing Connexin 40 (Cx40), abundantly expressed by these two cell types. Here, we generated mice with cell-specific deletion of Cx40 in endothelial and in renin-producing cells, as its global deletion caused local dissociation of renin-producing cells from endothelial cells, renin hypersecretion, and hypertension. In mice lacking endothelial Cx40, the blood pressure, renin-producing cell distribution, and the control of renin secretion were similar to wild-type mice. In contrast, mice deficient for Cx40 in renin-producing cells were hypertensive and these cells were ectopically localized. Although plasma renin activity and kidney renin mRNA levels of these mice were not different from controls, the negative regulation of renin secretion by pressure was inverted to a positive feedback in kidneys lacking Cx40 in renin-producing cells. Thus, our findings show that endothelial Cx40 is not essential for the control of renin expression and/or release. Cx40 in renin-producing cells is required for their correct positioning in the juxtaglomerular area and the control of renin secretion by pressure.
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DOI：
10.1152/ajpregu.00489.2007
发表时间：
2008-06-01
影响因子：
2.8
作者：
Toma, Ildiko;Bansal, Eric;Peti-Peterdi, Janos
通讯作者：
Peti-Peterdi, Janos
影响因子：
13.6
作者：
Kurtz, Lisa;Janssen-Bienhold, Ulrike;Wagner, Charlotte
通讯作者：
Wagner, Charlotte
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
影响因子：
19.6
作者：
Schweda, Frank;Kurtz, Lisa;Wagner, Charlotte
通讯作者：
Wagner, Charlotte
影响因子：
2.7
作者：
Kisanuki, YY;Hammer, RE;Yanagisawa, M
通讯作者：
Yanagisawa, M