V2 vasopressin receptor deficiency causes changes in expression and function of renal and hypothalamic components involved in electrolyte and water homeostasis.
V2 vasopressin receptor deficiency causes changes in expression and function of renal and hypothalamic components involved in electrolyte and water homeostasis.
复制标题
V2 加压素受体缺乏会导致涉及电解质和水稳态的肾脏和下丘脑成分的表达和功能发生变化。
DOI：
10.1152/ajprenal.00465.2007
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Sangkuhl,Katrin
中科院分区：
文献类型：
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作者：
Schliebe,Nicole;Strotmann,Rainer;Busse,Kathy;Mitschke,Doreen;Biebermann,Heike;Schomburg,Lutz;Kohrle,Josef;Bar,Jorg;Rompler,Holger;Wess,Jurgen;Schoneberg,Torsten;Sangkuhl,Katrin
多尿、高钠血症和低血容量是遗传性肾性尿崩症（NDI）的主要临床表现。高钠血症通常被认为是由水通道蛋白-2水通道插入集合管细胞顶膜不足引起的水净损失引起的继发性体征。在本研究中，我们采用全转录组表达分析来研究V2加压素受体（Avpr 2）缺陷小鼠（X连锁NDI的动物模型）的基因表达。NDI小鼠的基因表达变化表明近端肾小管钠重吸收增加。Na+-K+-ATP酶和碳酸酐酶等关键基因的表达在mRNA水平上增加，并伴随着酶活性的增强。此外，还观察到肾脏和下丘脑中类花生酸和甲状腺激素途径组分（包括环氧合酶和脱碘酶）的表达改变。这些效应可能促成临床NDI表型。最后，我们的数据强调参与NDI的病理生理学的肾素-血管紧张素-醛固酮系统，并提供线索来解释利尿剂和吲哚美辛在治疗NDI的有效性。
Polyuria, hypernatremia, and hypovolemia are the major clinical signs of inherited nephrogenic diabetes insipidus (NDI). Hypernatremia is commonly considered a secondary sign caused by the net loss of water due to insufficient insertion of aquaporin-2 water channels into the apical membrane of the collecting duct cells. In the present study, we employed transcriptome-wide expression analysis to study gene expression in V2 vasopressin receptor (Avpr2)-deficient mice, an animal model for X-linked NDI. Gene expression changes in NDI mice indicate increased proximal tubular sodium reabsorption. Expression of several key genes including Na+-K+-ATPase and carbonic anhydrases was increased at the mRNA levels and accompanied by enhanced enzyme activities. In addition, altered expression was also observed for components of the eicosanoid and thyroid hormone pathways, including cyclooxygenases and deiodinases, in both kidney and hypothalamus. These effects are likely to contribute to the clinical NDI phenotype. Finally, our data highlight the involvement of the renin-angiotensin-aldosterone system in NDI pathophysiology and provide clues to explain the effectiveness of diuretics and indomethacin in the treatment of NDI.