A role for Rhesus factor Rhcg in renal ammonium excretion and male fertility

A role for Rhesus factor Rhcg in renal ammonium excretion and male fertility
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DOI:
10.1038/nature07518
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发表时间:
2008-11-20
期刊:
影响因子:
64.8
通讯作者:
Marini, Anna Maria
Marini, Anna Maria
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Biver, Sophie;Belge, Hendrica;Marini, Anna Maria

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肾脏在调节酸碱平衡中起着重要作用.在基础条件下和代谢性酸中毒期间,肾铵的产生和排泄对于净酸排泄是必不可少的。铵通过集合管分泌到尿中,集合管是一个远端肾单位段,其中铵转运被认为通过非离子NH3扩散偶联H+分泌发生。在这里,我们表明,这一过程在很大程度上取决于恒河猴因子Rhcg。缺乏Rhcg的小鼠由于酸负荷下铵排泄受损而具有异常的尿酸化-远端肾小管酸中毒的特征。体外微灌注的Rhcg(-/-)酸负载小鼠的收集管显示对NH3的顶端渗透性降低和NH3跨上皮转运受损。此外,Rhcg位于附睾上皮细胞中,是正常生育能力和附睾液pH值所需的。我们预计Rhcg在肾脏和男性生殖道的铵处理和pH稳态中发挥关键作用。
The kidney has an important role in the regulation of acid - base homeostasis. Renal ammonium production and excretion are essential for net acid excretion under basal conditions and during metabolic acidosis. Ammonium is secreted into the urine by the collecting duct, a distal nephron segment where ammonium transport is believed to occur by non- ionic NH3 diffusion coupled to H+ secretion. Here we show that this process is largely dependent on the Rhesus factor Rhcg. Mice lacking Rhcg have abnormal urinary acidification due to impaired ammonium excretion on acid loading - a feature of distal renal tubular acidosis. In vitro microperfused collecting ducts of Rhcg(-/-) acid- loaded mice show reduced apical permeability to NH3 and impaired transepithelial NH3 transport. Furthermore, Rhcg is localized in epididymal epithelial cells and is required for normal fertility and epididymal fluid pH. We anticipate a critical role for Rhcg in ammonium handling and pH homeostasis both in the kidney and the male reproductive tract.