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Here, we show that FGF23 directly regulates the membrane abundance of the Na\n                    <jats:sup>+<\/jats:sup>\n                    :Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    co\u2010transporter NCC in distal renal tubules by a signaling mechanism involving the FGF receptor\/\u03b1Klotho complex, extracellular signal\u2010regulated kinase 1\/2 (ERK1\/2), serum\/glucocorticoid\u2010regulated kinase 1 (SGK1), and with\u2010no lysine kinase\u20104 (WNK4). Renal sodium (Na\n                    <jats:sup>+<\/jats:sup>\n                    ) reabsorption and distal tubular membrane expression of NCC are reduced in mouse models of\n                    <jats:italic>Fgf23<\/jats:italic>\n                    and \u03b1\n                    <jats:italic>Klotho<\/jats:italic>\n                    deficiency. Conversely, gain of FGF23 function by injection of wild\u2010type mice with recombinant FGF23 or by elevated circulating levels of endogenous Fgf23 in\n                    <jats:italic>Hyp<\/jats:italic>\n                    mice increases distal tubular Na\n                    <jats:sup>+<\/jats:sup>\n                    uptake and membrane abundance of NCC, leading to volume expansion, hypertension, and heart hypertrophy in a \u03b1Klotho and dietary Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010dependent fashion. The NCC inhibitor chlorothiazide abrogates FGF23\u2010induced volume expansion and heart hypertrophy. Our findings suggest that FGF23 is a key regulator of renal Na\n                    <jats:sup>+<\/jats:sup>\n                    reabsorption and plasma volume, and may explain the association of FGF23 with cardiovascular risk in chronic kidney disease patients.\n                  <\/jats:p>","DOI":"10.1002\/emmm.201303716","type":"journal-article","created":{"date-parts":[[2014,5,10]],"date-time":"2014-05-10T06:09:36Z","timestamp":1399702176000},"page":"744-759","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":308,"title":["FGF23 regulates renal sodium handling and blood pressure"],"prefix":"10.1038","volume":"6","author":[{"given":"Olena","family":"Andrukhova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Slavic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Smorodchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Zeitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Shalhoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Lanske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena E","family":"Pohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhold G","family":"Erben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,5,5]]},"reference":[{"key":"BFEMMM201303716_CR2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.bone.2012.05.015","volume":"51","author":"O Andrukhova","year":"2012","unstructured":"Andrukhova O, Zeitz U, Goetz R, Mohammadi M, Lanske B, Erben RG (2012) FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1\/2\u2010SGK1 signaling pathway. 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