Journal ArticleDOI
Molecular Mechanisms of Vitamin D Action
Mark R. Haussler,G. Kerr Whitfield,Ichiro Kaneko,Ichiro Kaneko,Carol A. Haussler,David Hsieh,Jui Cheng Hsieh,Peter W. Jurutka,Peter W. Jurutka +8 more
TLDR
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.Abstract:
The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D(3) (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, CaBP(9k), 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, eg, 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 cancerread more
Citations
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Journal ArticleDOI
Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.
TL;DR: The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange, which will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications.
Journal ArticleDOI
The role of vitamin D in reducing cancer risk and progression
TL;DR: Accumulating results from preclinical and some clinical studies strongly suggest that vitamin D deficiency increases the risk of developing cancer and that avoiding deficiency and adding vitamin D supplements might be an economical and safe way to reduce cancer incidence and improve cancer prognosis and outcome.
Journal ArticleDOI
Exploring vitamin D metabolism and function in cancer
Sang-Min Jeon,Eun-Ae Shin +1 more
TL;DR: The metabolic processes underlying the anti-cancer effects of vitamin D are summarized, ways to improve vitamin D-based therapies for cancer are discussed, and ideas to improve these therapies are discussed.
Journal ArticleDOI
MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19.
John P. Bilezikian,Daniel D. Bikle,Martin Hewison,Marise Lazaretti-Castro,Anna Maria Formenti,Aakriti Gupta,Aakriti Gupta,Mahesh V. Madhavan,Nandini Nair,Varta Babalyan,Nicholas Hutchings,Nicola Napoli,Nicola Napoli,Accili Domenico,Neil Binkley,Donald W. Landry,Andrea Giustina +16 more
TL;DR: The focus of this article is to apply the current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease.
Journal ArticleDOI
Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment
TL;DR: The biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment are described.
References
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Book
Vitamin D
TL;DR: In what case do you like reading so much? What about the type of the vitamin d the calcium homeostatic steroid hormone book? The needs to read? Well, everybody has their own reason why should read some books as discussed by the authors.
Journal ArticleDOI
Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Philip T. Liu,Steffen Stenger,Huiying Li,Linda Wenzel,Belinda H. Tan,Stephan R. Krutzik,Maria Teresa Ochoa,Jürgen Schauber,Kent Wu,Christoph Meinken,Diane L. Kamen,Manfred Wagner,Robert Bals,Andreas Steinmeyer,Ulrich Zügel,Richard L. Gallo,David Eisenberg,Martin Hewison,Bruce W. Hollis,John S. Adams,Barry R. Bloom,Robert L. Modlin +21 more
TL;DR: The data support a link between TLRs and vitamin D–mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.
Journal ArticleDOI
Endocrine Regulation of Energy Metabolism by the Skeleton
Na Kyung Lee,Hideaki Sowa,Eiichi Hinoi,Mathieu Ferron,Jong Deok Ahn,Cyrille Confavreux,Romain Dacquin,Patrick J. Mee,Marc D. McKee,Dae Young Jung,Zhiyou Zhang,Jason K. Kim,Franck Mauvais-Jarvis,Patricia Ducy,Gerard Karsenty +14 more
TL;DR: It is shown that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity, and in vivo osteocalcin can improve glucose tolerance.
Journal ArticleDOI
Nuclear receptors and lipid physiology: opening the X-files.
TL;DR: Some general principles that govern the actions of this class of bioactive lipids and their nuclear receptors are considered here, and the scheme that emerges reveals a complex molecular script at work.
Journal ArticleDOI
FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis.
Takashi Shimada,Hisashi Hasegawa,Yuji Yamazaki,Takanori Muto,Rieko Hino,Yasuhiro Takeuchi,Toshiro Fujita,Kazuhiko Nakahara,Seiji Fukumoto,Takeyoshi Yamashita +9 more
TL;DR: FGF‐23 is a potent regulator of the vitamin D and phosphate metabolism and caused a reduction in serum 1,25‐dihydroxyvitamin D by altering the expressions of key enzymes for the vitaminD metabolism followed by hypophosphatemia.
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Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Philip T. Liu,Steffen Stenger,Huiying Li,Linda Wenzel,Belinda H. Tan,Stephan R. Krutzik,Maria Teresa Ochoa,Jürgen Schauber,Kent Wu,Christoph Meinken,Diane L. Kamen,Manfred Wagner,Robert Bals,Andreas Steinmeyer,Ulrich Zügel,Richard L. Gallo,David Eisenberg,Martin Hewison,Bruce W. Hollis,John S. Adams,Barry R. Bloom,Robert L. Modlin +21 more