Connexin 43 is not essential for the control of renin synthesis and secretion
Connexin 43 is not essential for the control of renin synthesis and secretion
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DOI：
10.1007/s00424-013-1349-2
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发表时间：
2014-05-01
影响因子：
4.5
通讯作者：
Wagner, Charlotte
中科院分区：
文献类型：
--
作者：
Gerl, Melanie;Kurt, Birguel;Wagner, Charlotte
哺乳动物肾脏的肾小球旁区表达差距连接蛋白连接蛋白37、40、43和45。其中，Cx40在肾小球肾素表达细胞的功能中起着重要作用，而Cx 37和Cx45在这种情况下似乎不太相关。由于剩余的Cx43的作用，肾素表达的功能还没有很好地理解，本研究的目的是系统地表征的直接作用，Cx43的肾素表达和分泌。为了这个目的，我们产生的小鼠内皮细胞和与肾素细胞特异性缺失的Cx43，我们的特点是调节这些小鼠的肾脏中的肾素表达和分泌的正常盐饮食和慢性挑战期间的肾素系统预处理的小鼠与低盐饮食结合血管紧张素I转换酶抑制剂。我们发现，在基础条件下，野生型、Cx43（fl/fl）Ren 1d（+/Cre）小鼠以及Cx43（fl/fl）Tie-2（+/Cre）小鼠之间的肾脏肾素mRNA丰度、血浆肾素浓度和收缩压没有差异，在盐耗竭的慢性刺激下也没有差异。在所有基因型的肾脏中，肾素表达细胞的定位也是有规律的，而且，在Cx43（fl/fl）Ren 1d（+/Cre）和Cx43（fl/fl）Tie-2（+/Cre）小鼠的离体灌注肾脏中测量的β-肾上腺素能刺激和肾灌注压对肾素分泌的调节与对照没有差异。我们从这些结果中推断，Cx43在肾脏中的肾素产生细胞的功能控制中发挥的作用（如果有的话）是很小的。
The juxtaglomerular areas of mammalian kidneys express the gap junction proteins connexin 37, 40, 43, and 45. Among these, Cx40 plays a major role for the function of juxtaglomerular renin-expressing cells, while Cx37 and Cx45 appear to be less relevant in this context. Since the role of the remaining Cx43 for the function of renin expression is not well understood, this study aimed to systematically characterize the direct role of Cx43 for renin expression and secretion. For this aim, we generated mice with endothelium and with renin cell-specific deletions of Cx43, and we characterized the regulation of renin expression and renin secretion in the kidneys of these mice on normal salt diet and during chronic challenge of the renin system by pretreatment of mice with a low-salt diet in combination with an angiotensin I-converting enzyme inhibitor. We found that renal renin mRNA abundance, plasma renin concentration, and systolic blood pressure did not differ between wild-type, Cx43(fl/fl) Ren1d(+/Cre) mice as well as Cx43(fl/fl) Tie-2(+/Cre) mice under basal conditions nor under chronic stimulation by salt depletion. The localization of renin-expressing cells was also regular in kidneys of all genotypes, and moreover, regulation of renin secretion by beta-adrenergic stimulation and renal perfusion pressure measured in isolated perfused kidneys of Cx43(fl/fl) Ren1d(+/Cre) and Cx43(fl/fl) Tie-2(+/Cre) mice was not different from control. We infer from these results that Cx43 plays if at all only a minor role for the functional control of renin-producing cells in the kidney.