The phosphate transporter NaPi-IIa determines the rapid renal adaptation to dietary phosphate intake in mouse irrespective of persistently high FGF23 levels

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• 作者：Soline Bourgeois (1)
  Paola Capuano (1)
  Gerti Stange (1)
  Reto Mlemann (1)
  Heini Murer (1)
  Jg Biber (1)
  Carsten A. Wagner (1)
  
• 关键词：Phosphate adaption ; Proximal tubule ; Brush border membrane ; FGF23 ; PTH
• 刊名：Pfl¨1gers Archiv - European Journal of Physiology
• 出版年：2013
• 出版时间：November 2013
• 年：2013
• 卷：465
• 期：11
• 页码：1557-1572
• 全文大小：
• 作者单位：Soline Bourgeois (1)
  Paola Capuano (1)
  Gerti Stange (1)
  Reto Mlemann (1)
  Heini Murer (1)
  Jg Biber (1)
  Carsten A. Wagner (1)
  
  1. Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland
  
• ISSN：1432-2013

文摘

Renal reabsorption of inorganic phosphate (Pi) is mediated by the phosphate transporters NaPi-IIa, NaPi-IIc, and Pit-2 in the proximal tubule brush border membrane (BBM). Dietary Pi intake regulates these transporters; however, the contribution of the specific isoforms to the rapid and slow phase is not fully clarified. Moreover, the regulation of PTH and FGF23, two major phosphaturic hormones, during the adaptive phase has not been correlated. C57/BL6 and NaPi-IIa/ mice received 5days either 1.2% (HPD) or 0.1% (LPD) Pi-containing diets. Thereafter, some mice were acutely switched to LPD or HPD. Plasma Pi concentrations were similar under chronic diets, but lower when mice were acutely switched to LPD. Urinary Pi excretion was similar in C57/BL6 and NaPi-IIa/ mice under HPD. During chronic LPD, NaPi-IIa/ mice lost phosphate in urine compensated by higher intestinal Pi absorption. During the acute HPD-to-LPD switch, NaPi-IIa/ mice exhibited a delayed decrease in urinary Pi excretion. PTH was acutely regulated by low dietary Pi intake. FGF23 did not respond to low Pi intake within 8h whereas the phospho-adaptator protein FRS2necessary for FGF-receptor cell signaling was downregulated. BBM Pi transport activity and NaPi-IIa but not NaPi-IIc and Pit-2 abundance acutely adapted to diets in C57/BL6 mice. In NaPi-IIa/, Pi transport activity was low and did not adapt. Thus, NaPi-IIa mediates the fast adaptation to Pi intake and is upregulated during the adaptation to low Pi despite persistently high FGF23 levels. The sensitivity to FGF23 may be regulated by adapting FRS2abundance and phosphorylation.