
DOI . ORG {
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Title[redir]:
Molecular Mechanisms of Vitamin D Action | Calcified Tissue International
Description:
The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP9k, and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer.
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Keywords {🔍}
google, scholar, article, pubmed, cas, vitamin, receptor, haussler, mol, dihydroxyvitamin, bone, biol, cell, gene, hsieh, endocrinol, whitfield, jurutka, regulation, res, expression, biochem, cells, intestinal, calcium, phosphate, transcriptional, human, pike, cancer, receptors, nuclear, usa, thompson, sci, endocrinology, dna, acad, chem, molecular, vdr, genes, proc, natl, clin, kato, metabolism, kaneko, binding, signaling,
Topics {✒️}
ifn-gamma-mediated antimicrobial activity month download article/chapter ligand-activated vdr-rxr modulates parathyroid hormone-related protein tcf4/beta-catenin cistromes 25-hydroxyvitamin d3–1α-hydroxylase gene na/pi-ii transporters intestinal na+-dependent phosphate renal sodium-dependent phosphate pseudovitamin d-deficiency rickets nuclear factor-kappab ligand beta-glucuronidase klotho hydrolyzes hormone-induced transcriptional derepression 25-dihydroxyvitamin d-resistant rickets renal-gastrointestinal-skeletal axis 25-dihydroxyvitamin d3/vdr-mediated induction c-myc gene expression nanoscale-size bone samples hair-cycle-dependent expression 25-dihydroxyvitamin d3-induced differentiation beaudoin gm 3rd cardiac renin-angiotensin systems major bone-matrix proteins anti-aging klotho gene jui-cheng hsieh & peter 25-hydroxyvitamin d-24-hydroxylase vitamin d-responsive element avian intestinal calbindin-d28k full article pdf intact vdr-rxr complex multiple long-range enhancers idiopathic infantile hypercalcemia chick parathyroid glands human renal cells multiple distal enhancers gene expression induced privacy choices/manage cookies responsive element access decreases nfkappab activity neonatal rat brain 25-dihydroxyvitamin d3 receptors human napi-3 gene chemically induced tumorigenesis uv-induced tumorigenesis cystathionine beta-synthase mediate transcriptional repression increasing ikappabalpha levels stem cell differentiation regulate renal calcium related subjects
Questions {❓}
- Manson JE, Mayne ST, Clinton SK (2011) Vitamin D and prevention of cancer—ready for prime time?
- Milat F, Ng KW (2009) Is Wnt signalling the final common pathway leading to bone formation?
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headline:Molecular Mechanisms of Vitamin D Action
description:The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP9k, and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer.
datePublished:2012-07-11T00:00:00Z
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Coactivator
Corepressor
1α,25-Dihydroxyvitamin D3
Retinoid X receptor
Transcription
Vitamin D receptor
Vitamin D responsive element
Biochemistry
general
Endocrinology
Orthopedics
Cell Biology
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headline:Molecular Mechanisms of Vitamin D Action
description:The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP9k, and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer.
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Coactivator
Corepressor
1α,25-Dihydroxyvitamin D3
Retinoid X receptor
Transcription
Vitamin D receptor
Vitamin D responsive element
Biochemistry
general
Endocrinology
Orthopedics
Cell Biology
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