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VDR AND transcription

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https://www.readbyqxmd.com/read/28918929/vitamin-d-receptor-targeted-treatment-to-prevent-pathological-dedifferentiation-of-pancreatic-%C3%AE-cells-under-hyperglycaemic-stress
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28778065/1-25d3-differentially-suppresses-bladder-cancer-cell-migration-and-invasion-through-the-induction-of-mir-101-3p
#9
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...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765037/vitamin-d-effects-on-monocytes%C3%AC-ccl-2-il6-and-cd14-transcription-in-addison-s-disease-and-hla-susceptibility
#10
A U Kraus, M Penna-Martinez, G Meyer, K Badenhoop
Addisońs disease is a rare autoimmune disorder leading to adrenal insufficiency and life-long glucocorticoid dependency. Vitamin D receptor (VDR) polymorphisms and vitamin D deficiency predispose to Addisońs disease. Aim of the current study was, to investigate potential anti-inflammatory vitamin D effects on monocytes in Addisońs disease, focusing on inflammatory CCL-2 and IL6, as well on monocyte CD14 markers. Addisońs disease is genetically linked to distinct HLA susceptibility alleles. Therefore we analyzed, whether HLA genotypes differed for vitamin D effects on monocyte markers...
July 29, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28749078/vitamin-d-insufficiency-correlates-with-peripheral-b10-cells-in-patients-with-pituitary-tumours
#11
Weimin Wang, Li Fu, Shengli Li, Zhiming Xu, Peng Qiu, Tong-Jiang Xu, Wei Yang, Yu-Bao Zhang, Guang-Ming Xu, Xiang-Dong Lu, Xinggang Li
The mechanism of pituitary gland tumour (PGT) is unclear. Aberrant immune tolerance is associated with the pathogenesis of tumour. Vitamin D and vitamin D receptor (VDR) are involved in the immune regulation. Interleukin (IL)-10 is one of the important immune regulatory molecules. This study aims to elucidate the role of VDR in the regulation of IL-10 in peripheral B cells of PGT patients. In this study, the peripheral blood samples were collected from PGT patients and healthy subjects. B cells were purified from the blood samples and analysed by RT-qPCR and Western blotting...
July 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28736298/calcitriol-mediated-reduction-in-ifn-%C3%AE-output-in-t-cell-large-granular-lymphocytic-leukemia-requires-vitamin-d-receptor-upregulation
#12
M Paige Kulling, C Kristine Olson, L Thomas Olson, E Cait Hamele, N Kathryn Carter, J David Feith, P Thomas Loughran
Constitutively activated STAT1 and elevated IFN-γ are both characteristic of T cell large granular lymphocytic leukemia (T-LGLL), a rare incurable leukemia with clonal expansion of cytotoxic T cells due to defective apoptosis. Interferon gamma (IFN-γ) is an inflammatory cytokine that correlates with worse progression and symptomology in multiple autoimmune diseases and cancers. In canonical IFN-γ-STAT1 signaling, IFN-γ activates STAT1, a transcription factor, via phosphorylation of tyrosine residue 701 (p-STAT1)...
July 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28712921/selective-regulation-of-biological-processes-by-vitamin-d-based-on-the-spatio-temporal-cistrome-of-its-receptor
#13
Antonio Neme, Sabine Seuter, Carsten Carlberg
The transcription factor vitamin D receptor (VDR) is the exclusive nuclear target of the biologically active form of vitamin D (1,25(OH)2D3). In THP-1 human monocytes we obtained a highly accurate VDR cistrome after 2 and 24h ligand stimulation comprising >11,600 genomic loci, 78% of which were detected exclusively after 24h. In contrast, a group of 510 persistent VDR sites occurred at all conditions and some 2100 VDR loci were only transiently occupied. Machine learning and statistical analysis as well as a comparison with the re-analyzed B cell VDR cistrome indicated a subgroup of 339 highly conserved persistent VDR sites that were suited best for describing vitamin D-triggered gene regulatory scenarios...
July 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28710799/high-glucose-induces-o-glcnac-glycosylation-of-the-vitamin-d-receptor-vdr-in-thp1-cells-and-in-human-macrophages-derived-from-monocytes
#14
Fernando Hernández-Sánchez, Silvia Guzmán-Beltrán, María Teresa Herrera, Yolanda Gonzalez, Manuel Salgado, Guadalupe Fabian, Martha Torres
Chronic hyperglycemia increases the carbon flux through the hexosamine pathway, allowing the accumulation of UDP-GlcNAc. UDP-GlcNAc is the sugar donor for the enzyme-mediated protein glycosylation event known as OGlcNAcylation. This posttranslational modification targets several transcription factors implicated in glucose toxicity, insulin resistance, and diabetes. Vitamin D plays an important role in glucose homeostasis and insulin secretion through transcriptional mechanisms mediated by its receptor (VDR)...
July 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28707894/vitamin-d-receptor-regulates-amyloid-beta-1-42-production-with-protein-disulfide-isomerase-a3
#15
Duygu Gezen-Ak, Irem L Atasoy, Esin Candas, Merve Alaylioglu, Selma Yilmazer, Erdinc Dursun
The challenge of understanding the biology of neuronal amyloid processing could provide a basis for understanding the amyloid pathology in Alzheimer's disease (AD). Based on our previous studies we have suggested that AD might be the consequence of a hormonal imbalance in which the critical hormone is vitamin D. The present study primarily focused on the creation of a condition that prevents the genomic or non-genomic action of vitamin D by disrupting vitamin D receptors (VDR or PDIA3/1,25MARRS); the effects of these disruptions on the series of proteins involved in secretases that play a crucial role in amyloid pathology and on amyloid beta (Aβ) production in primary cortical neurons were observed...
July 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28698609/functional-analyses-of-a-novel-missense-and-other-mutations-of-the-vitamin-d-receptor-in-association-with-alopecia
#16
Mayuko Tamura, Michiyasu Ishizawa, Tsuyoshi Isojima, Samim Özen, Akira Oka, Makoto Makishima, Sachiko Kitanaka
Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is a rare disorder, caused by bialellic mutations of the vitamin D receptor (VDR) gene, sometimes associated with alopecia. The aim of this study is to elucidate the mechanism of functional disruption of a novel mutation, detected in a patient with HVDRR, comparing to other mutations with or without alopecia. The patient was a 2-year-old girl with alopecia, who was clinically diagnosed as HVDRR. Genetic analysis revealed a novel homozygous mutation, S360P, located in ligand binding domain (LBD)...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28669525/mechanisms-of-skin-toxicity-associated-with-metabotropic-glutamate-receptor-5-negative-allosteric-modulators
#17
Falgun Shah, Antonia F Stepan, Alison O'Mahony, Sharlene Velichko, Alexandra E Folias, Christopher Houle, Christopher L Shaffer, John Marcek, Jessica Whritenour, Robert Stanton, Ellen L Berg
Cutaneous reactions represent one of the most common adverse drug effects observed in clinical trials leading to substantial compound attrition. Three negative allosteric modulators (NAMs) of metabotropic glutamate receptors (mGluRs), which represent an important target for neurological diseases, developed by Pfizer, were recently failed in preclinical development due to delayed type IV skin hypersensitivity observed in non-human primates (NHPs). Here we employed large-scale phenotypic profiling in standardized panels of human primary cell/co-culture systems to characterize the skin toxicity mechanism(s) of mGluR5 NAMs from two different series...
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28660994/altered-expression-of-ctla-4-cd28-vdr-and-cd45-mrna-in-t-cells-of-patients-with-hashimoto-s-thyroiditis-a-pilot-study
#18
Stana Tokić, Mario Štefanić, Ivan Karner, Ljubica Glavaš-Obrovac
INTRODUCTION: CD28/T-cell receptor (TCR)/cytotoxic T-lymphocyte antigen 4 (CTLA4) complex controls T-cell tolerance and autoimmunity in Hashimoto's thyroiditis (HT). In addition, CD45 protein tyrosine phosphatase (PTPase) and vitamin D receptor (VDR) cooperatively interact with the TCR complex to affect autoimmune processes central to the pathogenesis of HT. Nevertheless, their role in HT aetiology has been less well established. In this study, we aimed to explore mRNA expression levels of CTLA4, CD28, CD45, and VDR in T-cells, across different outcomes of HT...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28636886/sirt1-enzymatically-potentiates-1-25-dihydroxyvitamin-d3-signaling-via-vitamin-d-receptor-deacetylation
#19
Marya S Sabir, Zainab Khan, Chengcheng Hu, Michael A Galligan, Christopher M Dussik, Sanchita Mallick, Angelika Dampf Stone, Shane F Batie, Elizabeth T Jacobs, G Kerr Whitfield, Mark R Haussler, Michael C Heck, Peter W Jurutka
The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1...
September 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28635660/diverse-regulation-of-vitamin-d-receptor-gene-expression-by-1-25-dihydroxyvitamin-d-and-atra-in-murine-and-human-blood-cells-at-early-stages-of-their-differentiation
#20
Sylwia Janik, Urszula Nowak, Agnieszka Łaszkiewicz, Anastasiia Satyr, Michał Majkowski, Aleksandra Marchwicka, Łukasz Śnieżewski, Klaudia Berkowska, Marian Gabryś, Małgorzata Cebrat, Ewa Marcinkowska
Vitamin D receptor (VDR) is present in multiple blood cells, and the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is essential for the proper functioning of the immune system. The role of retinoic acid receptor α (RARα) in hematopoiesis is very important, as the fusion of RARα gene with PML gene initiates acute promyelocytic leukemia where differentiation of the myeloid lineage is blocked, followed by an uncontrolled proliferation of leukemic blasts. RARα takes part in regulation of VDR transcription, and unliganded RARα acts as a transcriptional repressor to VDR gene in acute myeloid leukemia (AML) cells...
June 21, 2017: International Journal of Molecular Sciences
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