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VDR AND transcription

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https://www.readbyqxmd.com/read/28336823/-regulatory-mechanism-of-calcium-metabolism
#1
Keiichi Ozono
It is often difficult for terrestrial animals to take enough calcium. To maintain serum or extracellular calcium levels is very important for muscle and nerve function. Two major regulators to increase the serum calcium levels are parathyroid hormone(PTH)and vitamin D. PTH binds to the G protein coupling receptor, PTH1R, and increases intracellular cAMP levels. Impirement in the PTH signalling causes many diseases such as pseudohypoparathyroidism and acrodysostosis with hormone resistance. Vitamin D is activated to 1,25-dihydroxyvitamin D[1,25(OH)2D]by two steps of hydroxylation which occurs in the Liver and Kidney...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28335003/identification-of-genetic-variants-affecting-vitamin-d-receptor-binding-and-associations-with-autoimmune-disease
#2
Giuseppe Gallone, Wilfried Haerty, Giulio Disanto, Sreeram V Ramagopalan, Chris P Ponting, Antonio J Berlanga-Taylor
Large numbers of statistically significant associations between sentinel SNPs and case-control status have been replicated by genome-wide association studies. Nevertheless, few underlying molecular mechanisms of complex disease are currently known. We investigated whether variation in binding of a transcription factor, the vitamin D receptor (VDR) whose activating ligand vitamin D has been proposed as a modifiable factor in multiple disorders, could explain any of these associations. VDR modifies gene expression by binding DNA as a heterodimer with the Retinoid X receptor (RXR)...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28330721/changes-in-the-human-transcriptome-upon-vitamin-d-supplementation
#3
Yvonne Pasing, Christopher Graham Fenton, Rolf Jorde, Ruth Hracky Paulssen
Vitamin D is hydroxylated in the liver and kidneys to its active form, which can bind to the vitamin D receptor (VDR). The VDR is present in a wide variety of different cells types and tissues and acts as a transcription factor. Although activation of the VDR is estimated to regulate expression of up to 5% of the human genome, our study is the first analysing gene expression after supplementation in more than 10 subjects. Subjects of a randomized controlled trial (RCT) received either vitamin D3 (n47) in a weekly dose of 20,000 IU or placebo (n 47) for a period of three to five years...
March 19, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28325259/vitamin-d-analogues-potential-use-in-cancer-treatment
#4
REVIEW
Michael J Duffy, Alyson Murray, Naoise C Synnott, Norma O'Donovan, John Crown
The vitamin D receptor (VDR) is a member of the thyroid-steroid family of nuclear transcription factors. Following binding of the active form of vitamin D, i.e., 1,25(OH)2D3 (also known as calcitriol) and interaction with co-activators and co-repressors, VDR regulates the expression of several different genes. Although relatively little work has been carried out on VDR in human cancers, several epidemiological studies suggest that low circulating levels of vitamin D are associated with both an increased risk of developing specific cancer types and poor outcome in patients with specific diagnosed cancers...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28315703/molecular-endocrinology-of-vitamin-d-on-the-epigenome-level
#5
REVIEW
Carsten Carlberg
The molecular endocrinology of vitamin D is based on the facts that i) its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the nuclear receptor vitamin D receptor (VDR) and ii) the transcription factor VDR is the unique target of 1,25(OH)2D3 in the nucleus. Short-term alterations of the epigenome are primarily changes in the post-translational modification status of nucleosome-forming histone proteins, the consequences of which are i) a local increase or decrease in chromatin accessibility and ii) the activation or repression of gene transcription...
March 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28257826/structural-aspects-of-vitamin-d-endocrinology
#6
Natacha Rochel, Ferdinand Molnár
1α,25-Dihydroxvitamin D3 (1,25(OH)2D3) is the hormonally active form of vitamin D3. Its synthesis and its metabolites, their transport and elimination as well as action on transcriptional regulation involves the harmonic cooperation of diverse proteins with vitamin D binding capacities such as vitamin D binding protein (DBP), cytochrome P450 enzymes or the nuclear vitamin receptor (VDR). The genomic mechanism of 1,25(OH)2D3 action involves its binding to VDR that functionally acts as a heterodimer with retinoid X receptor...
February 28, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28250190/activation-of-nrf2-antioxidant-signaling-by-1-25-dihydroxycholecalciferol-prevents-leptin-induced-oxidative-stress-and-inflammation-in-human-endothelial-cells
#7
Thaisa M Teixeira, Danielly C da Costa, Angela C Resende, Christophe O Soulage, Flavia F Bezerra, Julio B Daleprane
Background: Obesity is associated with hyperleptinemia and endothelial dysfunction. Hyperleptinemia has been reported to induce both oxidative stress and inflammation by increasing reactive oxygen species production.Objective: The objective of this study was to determine the effects of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] against leptin-induced oxidative stress and inflammation in human endothelial cells.Methods: Small interfering RNA (siRNA) were used to knock down the expression of vitamin D receptor (VDR) in human umbilical vein endothelial cells (HUVECs)...
March 1, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28249598/the-prognostic-utility-of-the-transcription-factor-srf-in-docetaxel-resistant-prostate-cancer-in-vitro-discovery-and-in-vivo-validation
#8
D J Lundon, A Boland, M Prencipe, G Hurley, A O'Neill, E Kay, S T Aherne, P Doolan, S F Madden, M Clynes, C Morrissey, J M Fitzpatrick, R W Watson
BACKGROUND: Docetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists. Previous work by our group has shown complex changes in pro and anti-apoptotic proteins in the development of resistance to docetaxel...
March 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28242709/vitamin-d-receptor-regulates-autophagy-in-the-normal-mammary-gland-and-in-luminal-breast-cancer-cells
#9
Luz E Tavera-Mendoza, Thomas Westerling, Eric Libby, Andriy Marusyk, Laura Cato, Raymundo Cassani, Lisa A Cameron, Scott B Ficarro, Jarrod A Marto, Jelena Klawitter, Myles Brown
Women in North America have a one in eight lifetime risk of developing breast cancer (BC), and a significant proportion of these individuals will develop recurrent BC and will eventually succumb to the disease. Metastatic, therapy-resistant BC cells are refractory to cell death induced by multiple stresses. Here, we document that the vitamin D receptor (VDR) acts as a master transcriptional regulator of autophagy. Activation of the VDR by vitamin D induces autophagy and an autophagic transcriptional signature in BC cells that correlates with increased survival in patients; strikingly, this signature is present in the normal mammary gland and is progressively lost in patients with metastatic BC...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28231019/pro-inflammatory-cytokines-impair-vitamin-d-induced-host-defense-in-cultured-airway-epithelial-cells
#10
Jasmijn A Schrumpf, Gimano D Amatngalim, Joris B Veldkamp, Renate M Verhoosel, Dennis K Ninaber, Soledad R Ordonez, Anne M van der Does, Henk P Haagsman, Pieter S Hiemstra
Vitamin D is a regulator of host defense against infections and induces expression of the antimicrobial peptide hCAP18/LL-37. Vitamin D deficiency is associated with chronic inflammatory lung diseases and respiratory infections. However, it is incompletely understood if and how (chronic) airway inflammation affects vitamin D metabolism and action. We hypothesized that long-term exposure of primary bronchial epithelial cells (PBEC) to pro-inflammatory cytokines alters their vitamin D metabolism, antibacterial activity and expression of hCAP18/LL-37...
February 23, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28177523/association-between-genetic-variation-within-vitamin-d-receptor-dna-binding-sites-and-risk-of-basal-cell-carcinoma
#11
Yuan Lin, Harvind S Chahal, Wenting Wu, Hyunje G Cho, Katherine J Ransohoff, Hongji Dai, Jean Y Tang, Kavita Y Sarin, Jiali Han
An increasing number of studies have reported a protective association between vitamin D and cancer risk. The vitamin D endocrine system regulates transcriptional programs involved in inflammation, cell growth and differentiation through the binding of vitamin D receptor (VDR) to specific VDR elements. However, limited attention has been given to the role of variation within VDR binding sites in the development of basal cell carcinoma (BCC). Across 2,776 previously identified VDR binding sites, we identified 2,540 independent single-nucleotide polymorphisms (SNPs) and examined their associations with BCC risk in a genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054 controls from two data sets...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28166722/integration-of-vdr-genome-wide-binding-and-gwas-genetic-variation-data-reveals-co-occurrence-of-vdr-and-nf-%C3%AE%C2%BAb-binding-that-is-linked-to-immune-phenotypes
#12
Prashant K Singh, Patrick R van den Berg, Mark D Long, Angie Vreugdenhil, Laurie Grieshober, Heather M Ochs-Balcom, Jianmin Wang, Sylvie Delcambre, Sami Heikkinen, Carsten Carlberg, Moray J Campbell, Lara E Sucheston-Campbell
BACKGROUND: The nuclear hormone receptor superfamily acts as a genomic sensor of diverse signals. Their actions are often intertwined with other transcription factors. Nuclear hormone receptors are targets for many therapeutic drugs, and include the vitamin D receptor (VDR). VDR signaling is pleotropic, being implicated in calcaemic function, antibacterial actions, growth control, immunomodulation and anti-cancer actions. Specifically, we hypothesized that the biologically significant relationships between the VDR transcriptome and phenotype-associated biology could be discovered by integrating the known VDR transcription factor binding sites and all published trait- and disease-associated SNPs...
February 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28160341/vitamin-d-regulates-immunoglobulin-mucin-domain-molecule-4-expression-in-dendritic-cells
#13
Zhi-Qiang Liu, Mao-Gang Li, Xiao-Rui Geng, Jun Liu, Gui Yang, Shu-Qi Qiu, Zhi-Gang Liu, Ping-Chang Yang
BACKGROUND AND AIMS: Dendritic cell (DC)-derived immunoglobulin domain molecule (TIM)4 plays a critical role in the initiation of T helper (Th)2 polarization. Vitamin D (VitD) involves the regulation of a number of immune responses. This study tests a hypothesis that VitD regulates TIM4 expression in DCs. METHODS: Peripheral blood samples were collected from patients with allergic rhinitis (AR) and healthy subjects. DCs were isolated from the samples and analyzed for the expression of TIM4...
February 4, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28159673/ripk1-binds-to-vitamin-d-receptor-and-decreases-vitamin-d-induced-growth-suppression
#14
Waise Quarni, Panida Lungchukiet, Anfernee Tse, Pei Wang, Yuefeng Sun, Ravi Kasiappan, Jheng-Yu Wu, Xiaohong Zhang, Wenlong Bai
Receptor interacting protein kinase 1 (RIPK1) is an enzyme acting downstream of tumor necrosis factor alpha to control cell survival and death. RIPK1 expression has been reported to cause drug resistance in cancer cells, but so far, no published studies have investigated the role of RIPK1 in vitamin D signaling. In the present study, we investigated whether RIPK1 plays any roles in 1,25-dihydroxyvitamin D3 (1,25D3)-induced growth suppression. In our studies, RIPK1 decreased the transcriptional activity of vitamin D receptor (VDR) in luciferase reporter assays independent of its kinase activity, suggesting a negative role of RIPK1 in 1,25D3 action...
February 1, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28146070/decreased-expression-of-vitamin-d-receptor-affects-an-immune-response-in-primary-biliary-cholangitis-via-the-vdr-mirna155-socs1-pathway
#15
Agnieszka Kempinska-Podhorodecka, Malgorzata Milkiewicz, Urszula Wasik, Joanna Ligocka, Michał Zawadzki, Marek Krawczyk, Piotr Milkiewicz
Primary biliary cholangitis (PBC) is an immune-mediated cholestatic disease. Vitamin D receptor (VDR)-dependent signaling constrains an inflammatory response by targeting the miRNA155-SOCS1 (suppressor of cytokine signaling 1) axis. The VDR-miRNA155-SOCS1 pathway was investigated in the context of the autoimmune response associated with PBC. Human liver tissues from non-cirrhotic PBC (n = 22), cirrhotic PBC (n = 22), cirrhotic primary sclerosing cholangitis (PSC, n=13), controls (n = 23), and peripheral blood mononuclear cells (PBMC) obtained from PBC (n = 16) and PSC (n = 10) patients and healthy subjects (n = 11) were used for molecular analyses...
January 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28122601/inhibition-of-stat3-signaling-ameliorates-atrophy-of-the-soleus-muscles-in-mice-lacking-the-vitamin-d-receptor
#16
Suchitra D Gopinath
BACKGROUND: Although skeletal muscle wasting has long been observed as a clinical outcome of impaired vitamin D signaling, precise molecular mechanisms that mediate the loss of muscle mass in the absence of vitamin D signaling are less clear. To determine the molecular consequences of vitamin D signaling, we analyzed the role of signal transducer and activator of transcription 3 (Stat3) signaling, a known contributor to various muscle wasting pathologies, in skeletal muscles. METHODS: We isolated soleus (slow) and tibialis anterior (fast) muscles from mice lacking the vitamin D receptor (VDR(-/-)) and used western blot analysis, quantitative RTPCR, and pharmacological intervention to analyze muscle atrophy in VDR(-/-) mice...
January 25, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28115699/similarities-and-differences-in-the-transcriptional-control-of-expression-of-the-mouse-tslp-gene-in-skin-epidermis-and-intestinal-epithelium
#17
Krishna Priya Ganti, Atish Mukherji, Milan Surjit, Mei Li, Pierre Chambon
We previously reported that selective ablation of the nuclear receptors retinoid X receptor (RXR)-α and RXR-β in mouse epidermal keratinocytes (RXR-αβ(ep-/-)) or a topical application of active vitamin D3 (VD3) and/or all-trans retinoic acid (RA) on wild-type mouse skin induces a human atopic dermatitis-like phenotype that is triggered by an increased expression of the thymic stromal lymphopoietin (TSLP) proinflammatory cytokine. We demonstrate here that in epidermal keratinocytes, unliganded heterodimers of vitamin D receptor (VDR)/RXR-α and retinoic acid receptor-γ (RAR-γ)/RXR-β are bound as repressing complexes to their cognate DNA-binding sequence(s) (DBS) in the TSLP promoter regulatory region...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28104492/constitutively-active-ras-signaling-reduces-1-25-dihydroxyvitamin-d-mediated-gene-transcription-in-intestinal-epithelial-cells-by-reducing-vitamin-d-receptor-expression
#18
REVIEW
Marsha L DeSmet, James C Fleet
High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH)2D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH)2D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene...
January 16, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28101343/effect-of-1-25-oh-2d3-on-transdifferentiation-of-rat-renal-tubular-epithelial-cells-induced-by-high-glucose
#19
Hongtao Hu, Shen Xu, Shuang Hu, Yue Gao, Hua Shui
Deficiency in vitamin D and its active metabolite is a characteristic of chronic kidney diseases (CKDs). Previous studies have reported that 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D, can attenuate renal interstitial fibrosis. The present study aimed to explore the effect of 1,25(OH)2D3 on the transdifferentiation of NRK-52E rat renal tubular epithelial cells (RTECs) induced by high glucose, as well as the expression of vitamin D receptor (VDR) and production of angiotensin (Ang) II...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28089917/micrornas-and-dicer1-are-regulated-by-1-25-dihydroxyvitamin-d-in-prostate-stroma
#20
Shweta Dambal, Angeline A Giangreco, Andres M Acosta, Andrew Fairchild, Zachary Richards, Ryan Deaton, Dennis Wagner, Reinhold Vieth, Peter H Gann, Andre Kajdacsy-Balla, Theodorus Van der Kwast, Larisa Nonn
Vitamin D deficiency increases the risk of lethal prostate adenocarcinomas (PCa) and the majority of older men are deficient. Although PCa arises from the epithelium, the surrounding stroma has hormonal regulatory control over the epithelium and contributes to carcinogenesis. Herein, we describe regulation of microRNAs (miRs) by the active hormone dihydroxyvitamin D (1,25(OH)2D) in human prostate stroma. 1,25(OH)2D binds the vitamin D receptor (VDR) transcription factor to regulate gene expression, including miRs, which have emerged as potent regulators of protein expression...
March 2017: Journal of Steroid Biochemistry and Molecular Biology
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