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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bacchetta, Justine Zaritsky, Joshua J. Sea, Jessica L. Chun, Rene F. Lisse, Thomas S. Zavala, Kathryn Nayak, Anjali Wesseling-Perry, Katherine Westerman, Mark Hollis, Bruce W. Salusky, Isidro B. Hewison, Martin |
| Description | Author Affiliation: Bacchetta J ( Department of Orthopaedic Surgery, UCLA Orthopaedic Hospital, and.) |
| Abstract | The antibacterial protein hepcidin regulates the absorption, tissue distribution, and extracellular concentration of iron by suppressing ferroportin-mediated export of cellular iron. In CKD, elevated hepcidin and vitamin D deficiency are associated with anemia. Therefore, we explored a possible role for vitamin D in iron homeostasis. Treatment of cultured hepatocytes or monocytes with prohormone 25-hydroxyvitamin D or active 1,25-dihydroxyvitamin D decreased expression of hepcidin mRNA by 0.5-fold, contrasting the stimulatory effect of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D on related antibacterial proteins such as cathelicidin. Promoter-reporter and chromatin immunoprecipitation analyses indicated that direct transcriptional suppression of hepcidin gene (HAMP) expression mediated by 1,25-dihydroxyvitamin D binding to the vitamin D receptor caused the decrease in hepcidin mRNA levels. Suppression of HAMP expression was associated with a concomitant increase in expression of the cellular target for hepcidin, ferroportin protein, and decreased expression of the intracellular iron marker ferritin. In a pilot study with healthy volunteers, supplementation with a single oral dose of vitamin D (100,000 IU vitamin D2) increased serum levels of 25D-hydroxyvitamin D from 27±2 ng/ml before supplementation to 44±3 ng/ml after supplementation (P<0.001). This response was associated with a 34% decrease in circulating levels of hepcidin within 24 hours of vitamin D supplementation (P<0.05). These data show that vitamin D is a potent regulator of the hepcidin-ferroportin axis in humans and highlight a potential new strategy for the management of anemia in patients with low vitamin D and/or CKD. |
| File Format | HTM / HTML |
| ISSN | 10466673 |
| e-ISSN | 15333450 |
| DOI | 10.1681/ASN.2013040355 |
| Journal | Journal of the American Society of Nephrology |
| Issue Number | 3 |
| Volume Number | 25 |
| Language | English |
| Publisher | American Society of Nephrology |
| Publisher Date | 2014-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Nephrology Antimicrobial Cationic Peptides Metabolism Hepcidins Vitamin D Physiology 3t3 Cells Animals Cation Transport Proteins Ferritins Healthy Volunteers Hep G2 Cells Mice Pilot Projects Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Nephrology |
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