{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T20:07:05Z","timestamp":1779221225753,"version":"3.51.4"},"reference-count":66,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01DK132060"],"award-info":[{"award-number":["R01DK132060"]}]},{"name":"NIH","award":["R01DK123097"],"award-info":[{"award-number":["R01DK123097"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,17]]},"abstract":"<jats:p>\n                    Vitamin D regulates mineral homeostasis. The most biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), is synthesized by CYP27B1 from 25-dihydroxyvitamin D (25D) and is inactivated by CYP24A1. Human monogenic diseases and genome-wide association studies support a critical role for CYP24A1 in regulation of mineral homeostasis, but little is known about its tissue-specific effects. Here, we describe the responses of mice with inducible global deletion, kidney-specific, and intestine-specific deletion of\n                    <jats:italic>Cyp24a1<\/jats:italic>\n                    to dietary calcium challenge and chronic kidney disease (CKD). Global and kidney-specific\n                    <jats:italic>Cyp24a1<\/jats:italic>\n                    deletion caused similar syndromes of systemic vitamin D intoxication: elevated circulating 1,25D, 25D, and fibroblast growth factor 23 (FGF23), activation of vitamin D target genes in the kidney and intestine, hypercalcemia, and suppressed parathyroid hormone (PTH). In contrast, mice with intestine-specific\n                    <jats:italic>Cyp24a1<\/jats:italic>\n                    deletion demonstrated activation of vitamin D target genes exclusively in the intestine, despite no changes in systemic vitamin D levels. In response to a high calcium diet, PTH was suppressed, despite normal serum calcium. In mice with CKD, intestinal\n                    <jats:italic>Cyp24a1<\/jats:italic>\n                    deletion decreased PTH and FGF23 without precipitating hypercalcemia. These results implicate kidney CYP24A1 in systemic vitamin D regulation while independent local effects of intestinal CYP24A1 could be targeted to treat secondary hyperparathyroidism in CKD.\n                  <\/jats:p>","DOI":"10.1172\/jci179882","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T12:00:33Z","timestamp":1734436833000},"source":"Crossref","is-referenced-by-count":12,"title":["Intestinal Cyp24a1 regulates vitamin D locally independent of systemic regulation by renal Cyp24a1 in mice"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6314-0893","authenticated-orcid":true,"given":"Michaela A.A.","family":"Fuchs","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5544-1896","authenticated-orcid":true,"given":"Alexander","family":"Grabner","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."},{"name":"Division of Nephrology, Department of Medicine and"},{"name":"Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melody","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L.","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily J.","family":"Burke","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nejla","family":"Latic","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkataramana","family":"Thiriveedi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8851-1352","authenticated-orcid":true,"given":"Jatin","family":"Roper","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-211X","authenticated-orcid":true,"given":"Shintaro","family":"Ide","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koki","family":"Abe","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kitai","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3285-8613","authenticated-orcid":true,"given":"Tomokazu","family":"Souma","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1127-1442","authenticated-orcid":true,"given":"Myles","family":"Wolf","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA."},{"name":"Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA."},{"name":"Joan and Sanford I. 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