{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:47:46Z","timestamp":1791978466582,"version":"4.4.0"},"reference-count":73,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Intestinal absorption of phosphate proceeds via an active\/transcellular route mostly mediated by NaPi\u2010IIb\/<jats:italic>Slc34a2<\/jats:italic> and a poorly characterized passive\/paracellular pathway.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Intestinal phosphate absorption and expression of NaPi\u2010IIb are stimulated by 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> but whether NaPi\u2010IIb is the only target under hormonal control remains unknown.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We report that administration of 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> to wild\u2010type mice resulted in the expected increase in active transport of phosphate in jejunum, without changing paracellular fluxes. Instead, the same treatment failed to alter phosphate transport in intestinal\u2010depleted <jats:italic>Slc34a2<\/jats:italic>\u2010deficient mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In both genotypes, 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> induced similar hyperphosphaturic responses and changes in the plasma levels of FGF23 and PTH.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>While urinary phosphate loss induced by administration of 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> did not alter plasma phosphate, further studies should investigate whether chronic administration would lead to phosphate imbalance in mice with reduced active intestinal absorption.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Intestinal absorption of phosphate is stimulated by 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3.<\/jats:sub> At least two distinct mechanisms underlie phosphate absorption in the gut, an active transcellular transport requiring the Na<jats:sup>+<\/jats:sup>\/phosphate cotransporter NaPi\u2010IIb\/<jats:italic>Slc34a2<\/jats:italic>, and a poorly characterized paracellular passive pathway. 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> stimulates NaPi\u2010IIb expression and function, and loss of NaPi\u2010IIb reduces intestinal phosphate absorption. However, it is remains unknown whether NaPi\u2010IIb is the only target for hormonal regulation by 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub>. Here we compared the effects of intraperitoneal administration of 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> (2\u00a0days, once per day) in wild\u2010type and intestinal\u2010specific <jats:italic>Slc34a2<\/jats:italic>\u2010deficient mice, and analysed trans\u2010 <jats:italic>vs<\/jats:italic>. paracellular routes of phosphate absorption. We found that treatment stimulated active transport of phosphate only in jejunum of wild\u2010type mice, though NaPi\u2010IIb protein expression was upregulated in jejunum and ileum. In contrast, 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> administration had no effect in <jats:italic>Slc34a2<\/jats:italic>\u2010deficient mice, suggesting that the hormone specifically regulates NaPi\u2010IIb expression. In both groups, 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> elicited the expected increase of plasma fibroblast growth factor 23 (FGF23) and reduction of parathyroid hormone (PTH). Treatment resulted in hyperphosphaturia (and hypercalciuria) in both genotypes, though mice remained normophosphataemic. While increased intestinal absorption and higher FGF23 can trigger the hyperphosphaturic response in wild types, only higher FGF23 can explain the renal response in <jats:italic>Slc34a2<\/jats:italic>\u2010deficient mice. Thus, 1,25(OH)<jats:sub>2<\/jats:sub> vitamin D<jats:sub>3<\/jats:sub> stimulates intestinal phosphate absorption by acting on the active transcellular pathway mostly mediated by NaPi\u2010IIb while the paracellular pathway appears not to be affected.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp280345","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T11:16:37Z","timestamp":1605611797000},"page":"1131-1150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["1,25(OH)<sub>2<\/sub> vitamin D<sub>3<\/sub> stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine"],"prefix":"10.1113","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-0544","authenticated-orcid":false,"given":"Nati","family":"Hernando","sequence":"first","affiliation":[{"name":"Institute of Physiology University of Z\u00fcrich  Z\u00fcrich 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