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VDR AND transcription

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https://www.readbyqxmd.com/read/29287957/novel-vdr-antagonists-based-on-the-gw0742-scaffold
#1
Kelly A Teske, Jonathan W Bogart, Leggy A Arnold
The vitamin D receptor is a nuclear hormone receptor that regulates cell proliferation, cell differentiation and calcium homeostasis. The receptor is endogenously activated by 1,25-dihydroxyvitamin D3, which induces transcription of VDR targets genes regulated by coactivator binding. VDR antagonists and partial agonists have been developed based on the secosteroid scaffold of vitamin D. Only a few non-secosteroid VDR antagonists are known. Herein, we report the rational design of non-secosteroid VDR antagonists using GW0742 as a scaffold...
December 19, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29218094/mir-351-negatively-regulates-osteoblast-differentiation-of-mscs-induced-by-cholesten-3-one-through-targeting-vdr
#2
Qiuke Hou, Yongquan Huang, Yiwen Luo, Bin Wang, Yamei Liu, Rudong Deng, Saixia Zhang, Fengbin Liu, Dongfeng Chen
Our previous reports indicated that (+)-cholesten-3-one induces osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) by activating vitamin D receptor (VDR). However, whether and how miRNAs modulate osteogenic differentiation induced by (+)-cholesten-3-one have not been explored. In this study, miRNA array profiling and further validation by quantitative real-time PCR revealed that miR-351 was downregulated during (+)-cholesten-3-one-induced osteogenic differentiation of MSCs. Overexpression of miR-351 by miR-351 precursor transfection markedly inhibited the expression of osteoblast-specific genes, such as alkaline phosphatase (ALP), collagen type II, osteopontin (OPN), and runt-related transcription factor 2 (RUNX2), which consequently decreased a number of calcium mineralized nodules...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29186386/gene-expression-pattern-in-response-to-cholecalciferol-supplementation-highlights-cubilin-as-a-major-protein-of-25-oh-d-uptake-in-adipocytes-and-male-mice-white-adipose-tissue
#3
Lauriane Bonnet, Esma Karkeni, Charlène Couturier, Julien Astier, Julie Dalifard, Catherine Defoort, Ljubica Svilar, Jean-Charles Martin, Franck Tourniaire, Jean-François Landrier
It is well established that the active form of vitamin D, i.e. 1,25(OH)2D, regulates the expression of genes involved in its own metabolism and transport in the kidney, and possibly in the liver. However, little is known about the transcriptional impact of cholecalciferol supplementation on white adipose tissue (WAT) and adipocytes, which are a major site of vitamin D and 25(OH)D storage in the organism. To fill this gap, we investigated the impact of cholecalciferol supplementation in WAT via a panel of genes coding for enzymes and proteins involved in vitamin D metabolism and uptake...
November 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/29183808/the-vitamin-d-receptor-vdr-binds-to-the-nuclear-matrix-via-its-hinge-domain-a-potential-mechanism-for-the-reduction-in-vdr-mediated-transcription-in-mitotic-cells
#4
Xiaoying Cui, Renata Pertile, Darryl W Eyles
Vitamin D is best known for its regulation of calcium homeostasis. Vitamin D exerts its genomic actions via the vitamin D receptor (VDR). As a member of the superfamily of nuclear receptors, the VDR is primarily located within the nucleus of non-dividing cells. We show here that the VDR relocates from the nucleus into the cytoplasm across all stages of cell division in CHO cells. Furthermore, we show that the VDR is transcriptionally inert during cell division. In addition, 1α, 25 dihydroxyvitamin D (1,25(OH)2D3) promotes VDR binding to the nuclear matrix...
November 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29178579/vitamin-d-receptor-expression-in-canine-mammary-gland-and-relationship-with-clinicopathological-parameters-and-progesterone-oestrogen-receptors
#5
R Sánchez-Céspedes, M D Fernández-Martínez, A Raya, C Pineda, I López, Y Millán
The vitamin D receptor (VDR) belongs to the nuclear class II receptor family. VDR is a ligand transcription factor and mediates the actions of calcitriol, the active product of vitamin D synthesis. Nowadays, it is known that the biological actions of calcitriol include the capacity to modulate cancer features, such as proliferation and differentiation, apoptosis, angiogenesis, invasion and metastasis. VDR expression has been demonstrated in human breast cancer and vitamin D has emerged as a promising targeted therapy...
November 27, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29176823/vitamin-d-receptor-is-present-on-the-neuronal-plasma-membrane-and-is-co-localized-with-amyloid-precursor-protein-adam10-or-nicastrin
#6
Erdinç Dursun, Duygu Gezen-Ak
Our recent study indicated that vitamin D and its receptors are important parts of the amyloid processing pathway in neurons. Yet the role of vitamin D receptor (VDR) in amyloid pathogenesis is complex and all regulations over the production of amyloid beta cannot be explained solely with the transcriptional regulatory properties of VDR. Given that we hypothesized that VDR might exist on the neuronal plasma membrane in close proximity with amyloid precursor protein (APP) and secretase complexes. The present study primarily focused on the localization of VDR in neurons and its interaction with amyloid pathology-related proteins...
2017: PloS One
https://www.readbyqxmd.com/read/29127362/functional-analysis-of-vdr-gene-mutation-r343h-in-a-child-with-vitamin-d-resistant-rickets-with-alopecia
#7
Min-Hua Tseng, Shih-Ming Huang, Fu-Sung Lo, Jing-Long Huang, Chih-Jen Cheng, Hwei-Jen Lee, Shih-Hua Lin
The functional study of different mutations on vitamin D receptor (VDR) gene causing hereditary vitamin D-resistant rickets (HVDRR) remains limited. This study was to determine the VDR mutation and the mechanisms of this mutation-causing phenotype in a family with HVDRR and alopecia. Phenotype was analyzed, and in vitro functional studies were performed. The proband and his affected sister exhibited typical HVDRR with alopecia, and their biochemical and radiographic abnormalities but not alopecia responded to supraphysiological doses of active vitamin D3...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29110708/co-expression-of-1%C3%AE-hydroxylase-and-vitamin-d-receptor-in-human-articular-chondrocytes
#8
Ann Kristin Hansen, Yngve Figenschau, Inigo Zubiaurre-Martinez
BACKGROUND: The aim was to investigate whether resident chondrocytes in human articular cartilage and in subculture express vitamin D receptor (VDR) and the enzyme that hydroxylates the prohormone 25(OH)D3 to the active hormone 1α,25(OH)2D3, namely 1α-hydroxylase (CYP27B1). Any putative effects of vitamin D on chondrocytes were also explored. METHODS: Cartilage from human osteoarthritic knee joints, cultured chondrocytes and cells grown in 3D spheroids were examined for the expression of VDR and 1α-hydroxylase by PCR, Western blots and immunolabelling...
November 6, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29106686/the-identification-of-pivotal-transcriptional-factors-mediating-cell-responses-to-drugs-with-drug-induced-liver-injury-liabilities
#9
Falgun Shah, Alex Medvedev, Anne Mai Wassermann, Marian Brodney, Liying Zhang, Sergei Makarov, Robert V Stanton
Drug-induced liver injury (DILI) is a leading cause of drug attrition during drug development and a common reason for drug withdrawal from the market. The poor predictability of conventional animal-based approaches (Olson et al. 2000) necessitates the development of alternative testing approaches. Body of evidence associates DILI with the induction of stress-response genes in the liver cells (Yuan and Kaplowitz 2013). Here, we set out to identify signal transduction pathways predominantly involved in the regulation of gene transcription by DILI drugs...
November 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29074826/-update-on-recent-progress-in-vitamin-d-research-molecular-basis-of-epigenetic-regulation-by-vitamin-d-via-its-nuclear-receptor
#10
Shigeaki Kato, Kou-Ichi Nishimura, Jin-Ichi Mori
Environment and structure of chromatin underlie epigenetics, and they also facilitate transcriptional regulations by nuclear receptors including VDR. In this short review, the molecular basis of chromatin remodeling and post-translational modifications of histone proteins are illustrated with characterization of their regulators, providing mechanisms for co-regulation of epigenetics and transcription on chromatin. Moreover, the role of enhancer RNA (eRNA), one of the non-coding RNAs, in chromatin configuration is discussed for gene regulation by VDR...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29074825/-update-on-recent-progress-in-vitamin-d-research-vitamin-d-receptor-and-the-nuclear-receptor-superfamily
#11
Makoto Makishima
The vitamin D receptor(VDR)is a ligand-dependent transcription factor of the nuclear receptor superfamily. VDR belongs to the NR1I subfamily along with other nuclear receptors involved in xenobiotic metabolism, such as pregnane X receptor. The oxysterol receptors liver X receptors α/β and the bile acid receptor farnesoid X receptor belong to the NR1H subfamily, which are closely related to the NR1I subfamily. NR1I and NR1H nuclear receptors form heterodimers with retinoid X receptor. The active form of vitamin D, 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], acts as a physiological VDR ligand, and regulates various physiological processes, including calcium and bone metabolism, cellular growth and differentiation, immunity, and cardiovascular function...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/29072505/profiling-of-anthocyanidins-against-transcriptional-activities-of-steroid-and-nuclear-receptors
#12
Barbora Pastorková, Petr Illés, Zdeněk Dvořák
The aim of current study was to evaluate the effect of the most common anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, and peonidin) on the transcriptional activity of steroid and nuclear receptors. The activities of steroid receptors - progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), and nuclear receptors - vitamin D receptor (VDR), retinoid X receptor (RXR), retinoic acid receptor (RAR), pregnane X receptor (PXR), and thyroid receptor (TR) were assessed using either stable transfected luciferase gene reporter cell lines or transiently transfected cell lines...
October 26, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29067439/apolipoprotein-m-increases-the-expression-of-vitamin-d-receptor-mrna-in-colorectal-cancer-cells-detected-with-duplex-fluorescence-reverse-transcription-quantitative-polymerase-chain-reaction
#13
Miao-Mei Yu, Shuang Yao, Kai-Ming Luo, Qin-Feng Mu, Yang Yu, Guang-Hua Luo, Ning Xu
Apolipoprotein M (ApoM) and the vitamin D receptor (VDR) are apolipoproteins predominantly presenting in high-density lipoprotein (HDL) and a karyophilic protein belonging to the steroid‑thyroid receptor superfamily, respectively. Previous studies have demonstrated that ApoM and VDR are associated with cholesterol metabolism, immune and colorectal cancer regulation. In order to investigate whether ApoM affected the expression of VDR in colorectal cancer cells, a single‑tube duplex fluorescence reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) system was developed to simultaneously detect the mRNA levels of VDR and GAPDH in HT‑29 cells overexpressing ApoM...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29061851/hormonal-vitamin-d-up-regulates-tissue-specific-pd-l1-and-pd-l2-surface-glycoprotein-expression-in-humans-but-not-mice
#14
Vassil Dimitrov, Manuella Bouttier, Giselle Boukhaled, Reyhaneh Salehi-Tabar, Radu G Avramescu, Babak Memari, Benedeta Hasaj, Gergely L Lukacs, Connie M Krawczyk, John H White
PD-L1 (programmed death ligand 1) and PD-L2 are cell-surface glycoproteins that interact with programmed death 1 (PD-1) on T cells to attenuate inflammation. PD-1 signaling has attracted intense interest for its role in a pathophysiological context: suppression of anti-tumor immunity. Similarly, vitamin D signaling has been increasingly investigated for its non-classical actions in stimulation of innate immunity and suppression of inflammatory responses. Here, we show that hormonal 1,25-dihydroxyvitamin D (1,25D) is a direct transcriptional inducer of the human genes encoding PD-L1 and PD-L2 through the vitamin D receptor, a ligand-regulated transcription factor...
December 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29050663/vitamin-d-deficiency-induces-eosinophil-spontaneous-activation
#15
Huiying Lu, Rui-Di Xie, Ritian Lin, Cuicui Zhang, Xiao-Jun Xiao, Lin-Jing Li, Zhi-Qiang Liu, Li-Tao Yang, Bai-Sui Feng, Zhan-Ju Liu, Ping-Chang Yang
Eosinophils (Eo) play a critical role in immunity and immune inflammation. The maintenance of Eo homeostasis is not fully understood yet. Vitamin D (VitD) is involved in the regulation of a large number of biochemical reactions. This study tests a hypothesis that VitD receptor (VDR) contributes to the homeostasis of Eos. In this study, EoL-1 cells (an Eo cell line) were cultured in the presence or absence of calcitriol. The Eo-mediators, including major basic protein (MBP), Eo peroxidase (EPX), Eo cationic protein (ECP) and Eo-derived neurotoxin (EDN), were assessed in the culture supernatant and in EoL-1 cells...
October 12, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29030554/hdx-reveals-the-conformational-dynamics-of-dna-sequence-specific-vdr-co-activator-interactions
#16
Jie Zheng, Mi Ra Chang, Ryan E Stites, Yong Wang, John B Bruning, Bruce D Pascal, Scott J Novick, Ruben D Garcia-Ordonez, Keith R Stayrook, Michael J Chalmers, Jeffrey A Dodge, Patrick R Griffin
The vitamin D receptor/retinoid X receptor-α heterodimer (VDRRXRα) regulates bone mineralization via transcriptional control of osteocalcin (BGLAP) gene and is the receptor for 1α,25-dihydroxyvitamin D3 (1,25D3). However, supra-physiological levels of 1,25D3 activates the calcium-regulating gene TRPV6 leading to hypercalcemia. An approach to attenuate this adverse effect is to develop selective VDR modulators (VDRMs) that differentially activate BGLAP but not TRPV6. Here we present structural insight for the action of a VDRM compared with agonists by employing hydrogen/deuterium exchange...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28947955/1-25d3-differentially-suppresses-bladder-cancer-cell-migration-and-invasion-through-the-induction-of-mir-101-3p
#17
Yingyu Ma, Wei Luo, Brittany L Bunch, Rachel N Pratt, Donald L Trump, Candace S Johnson
Metastasis is the major cause of bladder cancer death. 1,25D3, the active metabolite of vitamin D, has shown anti-metastasis activity in several cancer model systems. However, the role of 1,25D3 in migration and invasion in bladder cancer is unknown. To investigate whether 1,25D3 affects migration and invasion, four human bladder cell lines with different reported invasiveness were selected: low-invasive T24 and 253J cells and highly invasive 253J-BV and TCCSUP cells. All of the four bladder cancer cells express endogenous and inducible vitamin D receptor (VDR) as examined by immunoblot analysis...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938596/vitamin-d3-induces-vitamin-d-receptor-and-hdac11-binding-to-relieve-the-promoter-of-the-tight-junction-proteins
#18
Feng-Hua Liu, Shan-Shan Li, Xiao-Xi Li, Shuai Wang, Mao-Gang Li, Li Guan, Tian-Gang Luan, Zhi-Gang Liu, Zhan-Ju Liu, Ping-Chang Yang
Intestinal epithelial barrier dysfunction and vitamin D (VitD)-deficiency play a critical role in a large number of diseases. The histone deacetylases (HDAC) are associated with a large number of immune diseases. This study tests a hypothesis that the interaction between VitD and HDAC is associated with the regulation of epithelial barrier functions. In this study, human intestinal epithelial cell line, T84 cells, was cultured into monolayers to be used as a model to test the epithelial barrier functions. We observed that in a VitD-deficient environment, the T84 monolayer barrier function was compromised...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28918929/vitamin-d-receptor-targeted-treatment-to-prevent-pathological-dedifferentiation-of-pancreatic-%C3%AE-cells-under-hyperglycaemic-stress
#19
A Neelankal John, Z Iqbal, S Colley, G Morahan, M Makishima, F-X Jiang
Dedifferentiation has been identified as one of the causes of β-cell failure resulting in type 2 diabetes (T2D). This study tested whether increasing vitamin D receptor (VDR) expression prevents dedifferentiation of β cells in a high-glucose state in vitro. Culturing a mouse insulinoma cell line (MIN6) in a high-glucose environment decreased VDR expression. However, increased VDR following vitamin D3 (VD3) treatment improved insulin release of early-passage MIN6 and insulin index of db/- (heterozygous) islets to levels seen in normal functional islets...
September 11, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28915830/biological-effects-of-combined-resveratrol-and-vitamin-d3-on-ovarian-tissue
#20
Francesca Uberti, Vera Morsanuto, Silvio Aprile, Sabrina Ghirlanda, Ian Stoppa, Andrea Cochis, Giorgio Grosa, Lia Rimondini, Claudio Molinari
BACKGROUND: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural antioxidant polyphenol able to exert a wide range of biological effect on several tissues. Despite its important beneficial properties, it has a low water solubility, which limits its therapeutic applications in humans. Resveratrol also acts as a phytoestrogen that modulates estrogen receptor (ER)-mediated transcription. In addition, it has been shown that ovarian tissues benefit greatly from vitamin D3, which exerts its beneficial effects through VDR receptors...
September 15, 2017: Journal of Ovarian Research
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