Kidney collecting duct acid-base "regulon"
Kidney collecting duct acid-base "regulon"
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DOI：
10.1152/physiolgenomics.00069.2006
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发表时间：
2006-11-27
影响因子：
4.6
通讯作者：
Doucet, Alain
中科院分区：
文献类型：
--
作者：
Cheval, Lydie;Morla, Luciana;Doucet, Alain
肾脏对酸碱平衡至关重要，特别是当生物体应对酸或碱饮食摄入的变化时。由于收集管是调节尿酸碱平衡的最终位点，我们进行了小鼠外髓收集管（OMCD）中参与酸碱转运和调节的基因网络的鉴定。为此，我们通过转录组和候选基因方法，结合代谢性酸中毒期间omcd的肾功能研究和基因表达的定量分析。此外，为了更好地描述与酸碱失调有关的一组基因，我们将酸中毒小鼠的OMCD转录组与正常小鼠和通过钾耗竭进行适应性反应的小鼠进行了比较。通过添加nh4cl 3天的饮食，代谢性酸中毒不仅引起酸分泌，而且刺激醛固酮和加压素系统，引发细胞增殖。因此，代谢性酸中毒增加了参与酸碱转运、钠转运、水转运和细胞增殖的基因的表达。特别是，编码尿酸化蛋白的bbbb25转录本（h - atp酶亚基、肾阴离子交换器、氯通道Clcka、碳酸酐酶-2、醛缩酶）在酸中毒过程中被共同调节。这些转录本相互合作实现类似的功能，并在酸中毒过程中受到共同调控，构成了一个功能单元，我们建议将其称为“调控子”。
Kidneys are essential for acid-base homeostasis, especially when organisms cope with changes in acid or base dietary intake. Because collecting ducts constitute the final site for regulating urine acid-base balance, we undertook to identify the gene network involved in acid-base transport and regulation in the mouse outer medullary collecting duct (OMCD). For this purpose, we combined kidney functional studies and quantitative analysis of gene expression in OMCDs, by transcriptome and candidate gene approaches, during metabolic acidosis. Furthermore, to better delineate the set of genes concerned with acid-base disturbance, the OMCD transcriptome of acidotic mice was compared with that of both normal mice and mice undergoing an adaptative response through potassium depletion. Metabolic acidosis, achieved through an NH4Cl-supplemented diet for 3 days, not only induced acid secretion but also stimulated the aldosterone and vasopressin systems and triggered cell proliferation. Accordingly, metabolic acidosis increased the expression of genes involved in acid-base transport, sodium transport, water transport, and cell proliferation. In particular, > 25 transcripts encoding proteins involved in urine acidification (subunits of H-ATPase, kidney anion exchanger, chloride channel Clcka, carbonic anhydrase-2, aldolase) were co-regulated during acidosis. These transcripts, which cooperate to achieve a similar function and are co-regulated during acidosis, constitute a functional unit that we propose to call a "regulon".