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VDR AND transcription

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https://www.readbyqxmd.com/read/29127362/functional-analysis-of-vdr-gene-mutation-r343h-in-a-child-with-vitamin-d-resistant-rickets-with-alopecia
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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-upregulates-tissue-specific-pd-l1-and-pd-l2-surface-glycoprotein-expression-in-human-but-not-mouse
#8
Vassil Dimitrov, Manuella Bouttier, Giselle Boukhaled, Reyhaneh Salehi-Tabar, Radu Avramescu, Babak Memari, Benedeta Hasaj, Gergely L Lukacs, Connie Michele Krawczyk, John Howard 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 (VDR), a ligand-regulated transcription factor...
October 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29050663/vitamin-d-deficiency-induces-eosinophil-spontaneous-activation
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28900196/characterization-of-a-new-pathway-that-activates-lumisterol-in-vivo-to-biologically-active-hydroxylumisterols
#15
Andrzej T Slominski, Tae-Kang Kim, Judith V Hobrath, Zorica Janjetovic, Allen S W Oak, Arnold Postlethwaite, Zongtao Lin, Wei Li, Yukimasa Takeda, Anton M Jetten, Robert C Tuckey
Using LC/qTOF-MS we detected lumisterol, 20-hydroxylumisterol, 22-hydroxylumisterol, 24-hydroxylumisterol, 20,22-dihydroxylumisterol, pregnalumisterol, 17-hydroxypregnalumisterol and 17,20-dihydroxypregnalumisterol in human serum and epidermis, and the porcine adrenal gland. The hydroxylumisterols inhibited proliferation of human skin cells in a cell type-dependent fashion with predominant effects on epidermal keratinocytes. They also inhibited melanoma proliferation in both monolayer and soft agar. 20-Hydroxylumisterol stimulated the expression of several genes, including those associated with keratinocyte differentiation and antioxidative responses, while inhibiting the expression of others including RORA and RORC...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893622/differential-expression-of-vitamin-d-associated-enzymes-and-receptors-in-brain-cell-subtypes
#16
Véréna Landel, Delphine Stephan, Xiaoying Cui, Darryl Eyles, François Feron
Accumulating evidence indicates that the active form of vitamin D, 1,25(OH)2D3, can be considered as a neurosteroid. However, the cerebral expression of vitamin D-associated enzymes and receptors remains controversial. With the idea of carrying out a comparative study in mind, we compared the transcript expression of Cyp27a1, Cyp27b1, Cyp24a1, Vdr and Pdia3 in purified cultures of astrocytes, endothelial cells, microglia, neurons and oligodendrocytes. We observed that endothelial cells and neurons can possibly transform the inactive cholecalciferol into 25(OH)D3...
September 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28878195/1-945-25-dihydroxyvitamin-d3-attenuates-tgf-946-induced-pro-fibrotic-effects-in-human-lung-epithelial-cells-through-inhibition-of-epithelial-mesenchymal-transition
#17
Fei Jiang, Yong Yang, Lian Xue, Bingyan Li, Zengli Zhang
Pulmonary fibrosis is a progressive fibrotic lung disease of persisting lung injury and ineffective wound repair, with poor prognosis. Epithelial-mesenchymal transition (EMT) of alveolar epithelia cells is an early event in the development of pulmonary fibrosis, and transforming growth factor β (TGF-β) is an acknowledged inducer of EMT. Epidemiological studies demonstrated that serum levels of 25-hydroxy-vitamin D were associated with the presence of fibrosis diseases. We investigated whether vitamin D attenuated TGF-β-induced pro-fibrotic effects through inhibiting EMT in human alveolar epithelia A549 cells...
September 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28870774/ets-transcription-factor-family-member-gabpa-contributes-to-vitamin-d-receptor-target-gene-regulation
#18
Sabine Seuter, Antonio Neme, Carsten Carlberg
Binding motifs of the ETS-domain transcription factor GABPA are found with high significance below the summits of the vitamin D receptor (VDR) cistrome. VDR is the nuclear receptor for the biologically most active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). In this study, we determined the GABPA cistrome in THP-1 human monocytes and found that it is comprised of 3822 genomic loci, some 20% of which were modulated by 1,25(OH)2D3. The GABPA cistrome showed a high overlap rate with accessible chromatin and the pioneer transcription factor PU...
September 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28814738/identification-of-novel-non-secosteroidal-vitamin-d-receptor-agonists-with-potent-cardioprotective-effects-and%C3%A2-%C3%AF-%C3%AF-devoid-of-hypercalcemia
#19
Santosh A Khedkar, Mohammed A Samad, Sangita Choudhury, Ji Yoo Lee, Dongsheng Zhang, Ravi I Thadhani, S Ananth Karumanchi, Alan C Rigby, Peter M Kang
Vitamin D regulates many biological processes, but its clinical utility is limited by its hypercalcemic effect. Using a virtual screening platform to search novel chemical probes that activate the vitamin D signaling, we report discovery of novel non-steroidal small-molecule compounds that activate the vitamin D receptor (VDR), but are devoid of hypercalcemia. A lead compound (known as VDR 4-1) demonstrated potent transcriptional activities in a VDR reporter gene assay, and significantly ameliorated cardiac hypertrophy in cell culture studies and in animal models...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#20
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
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