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Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase

Hewison, M; Zehnder, D; Chakraverty, R; Adams, JS; (2004) Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase. MOLECULAR AND CELLULAR ENDOCRINOLOGY , 215 (1-2) 31 - 38. 10.1016/j.mce.2003.11.017.

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Abstract

Much recent attention has focused on the positive health benefits of vitamin D beyond its established role in calcium homeostasis. Epidetmology has highlighted the link between vitamin D deficiency and prevalent diseases such as common cancers and autoimmune disease. Furthermore, studies in vitro have shown that the active form of vitamin D, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) is a potent antiproliferative and itnmunosuppressive agent. The net effect of this has been the generation and analysis of synthetic analogues of vitamin D for potential use in the treatment of cancers and other disorders including psoriasis. However, there is increasing interest in the impact that vitamin D may have on normal physiology above and beyond its classical effects on calcium homeostasis and bone metabolism. We have postulated that these `non-calcetnic' effects of vitamin D are dependent on extra-renal synthesis of 1,25(OH)2D3 via the enzyme la-hydroxylase at barrier sites throughout the body. Here we present a review of the mechanisms associated with extra-renal 1 a-hydroxylase, and we also speculate on how this `new' physiological role for vitamin D may actually reflect an ancient function for this pluripotent secosteroid. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Type: Article
Title: Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase
Location: Bath, ENGLAND
DOI: 10.1016/j.mce.2003.11.017
Keywords: vitamin D, 1 alpha-hydroxylase, extra-renal, macrophage, dendritic cell, epithelial cell, TOLL-LIKE RECEPTORS, PROTEIN-KINASE-C, 25-HYDROXYVITAMIN D-3-1-ALPHA-HYDROXYLASE, 1,25-DIHYDROXYVITAMIN D-3, ALVEOLAR MACROPHAGES, ABNORMAL REGULATION, PROSTATE-CANCER, GENE-EXPRESSION, BREAST-CANCER, D METABOLITES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1306920
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