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Kidney collecting duct acid-base "regulon"

¹ Laboratoire de Physiologie et Génomique Rénales, Unité mixte de recherche 7134 Centre National de la Recherche Scientifique/Université Pierre et Marie Curie, Institut Fédératif de Recherche 58, Institut des Cordeliers, 15 rue de l'Ecole de Médecine, 75270 Paris cedex 6, France
² Département de Biologie Joliot Curie, Commissariat à l'Énergie Atomique, 91191 Gif sur Yvette cedex, France

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".

serial analysis for gene expression; mouse; metabolic acidosis; V-ATPase

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