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VDR AND transcription

Franziska Just, Michael Oster, Kirsten Büsing, Luisa Borgelt, Eduard Murani, Siriluck Ponsuksili, Petra Wolf, Klaus Wimmers
BACKGROUND: In monogastric animals, phosphorus (P) homeostasis is maintained by regulating intestinal absorption, bone mobilization, and renal excretion. Since P is a non-renewable resource, a shortage is imminent due to widespread over-usage in the farming and animal husbandry industries. As a consequence, P efficiency should be improved in pig production. We sought to characterize the transcriptional response in re-/absorbing and excreting tissues in pigs to diets varying in calcium: phosphorus ratios...
March 20, 2018: BMC Genomics
Hyun-Soo Kim, Mingzhen Zheng, Do-Kyung Kim, Won-Pyo Lee, Sang-Joun Yu, Byung-Ock Kim
Purpose: The purpose of this study was to evaluate the effects of 1,25-dihydroxyvitamin D3 on the proliferation, differentiation, and matrix mineralization of MC3T3-E1 osteoblast-like cells in vitro. Methods: MC3T3-E1 osteoblastic cells and 1,25-dihydroxyvitamin D3 were prepared. Cytotoxic effects and osteogenic differentiation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) activity assay, ALP staining, alizarin red S staining, and reverse transcription-polymerase chain reaction (RT-PCR) for osteogenic differentiation markers such as ALP, collagen type I (Col-I), osteocalcin (OCN), vitamin D receptor (VDR), and glyceraldehyde 3-phosphate dehydrogenase...
February 2018: Journal of Periodontal & Implant Science
M Herian, M R Luck, M Grzesiak
Recently it has been shown that vitamin D(3) acting via its cognate receptor (VDR) regulates the growth, differentiation and function of female reproductive tissues including ovary. The aim of the study was to examine the effect of testosterone (T) and its antagonist 2-hydroxyflutamide (HF) on VDR protein expression and function in porcine ovarian follicles. Medium size antral follicles expressing great amount of androgen receptors and represent high steroidogenic activity were used in this research. After 6 h incubation of whole follicles with T, HF or T+HF, immunohistochemical analysis of VDR revealed its nuclear localization in granulosa and theca interna cells in control and experimental groups...
March 12, 2018: Physiological Research
Harrison T Supnick, Rodica P Bunaciu, Andrew Yen
Differentiation therapy is used in cancer treatment. Epidemiologic studies showed that higher vitamin D levels are associated with reduced cancer risks. However, the therapeutic doses needed for differentiation are accompanied by hypercalcemia and intolerable pathological sequelae. In the present work we evaluated if RRD-251, a small-molecule, can enhance vitamin D3-induced differentiation of leukemic cells, in the hope of decreasing the needed vitamin D3-dose. We demonstrate that RRD-251 enhances vitamin D3-induced differentiation of leukemic cells, the enrichment of the c-Raf kinase in the nucleus, the binding of nuclear c-Raf to GSK-3, increased phosphorylation of GSK-3 ser 21/9 inhibitory sites, and the binding of GSK-3 to VDR, where GSK-3 inhibition is known to enhance transcriptional activation by VDR...
February 9, 2018: Oncotarget
Iveta Bartonkova, Enikoe Kallay, Zdenek Dvorak
The role of vitamin D receptor (VDR) in immune responses has been broadly studied and it has been shown that activated VDR alters the levels of some interleukins (ILs). In this study, we studied the opposite, i.e. whether 13 selected pro-inflammatory and anti-inflammatory ILs influence the transcriptional activity of human VDR. The experimental models of choice were two human stably transfected gene reporter cell lines IZ-VDRE and IZ-CYP24, which were designed to evaluate the transcriptional activity of VDR...
2018: PloS One
K N Liu, H X Meng, J X Hou
OBJECTIVE: There is asingle nucleotide polymorphism (SNP) in the exon 2 of the vitamin D receptor (VDR) gene that can be distinguished using the restriction endonuclease FokI, and accordingly divided into three genotypes: FF, Ff and ff. VDR-FokI polymorphism was the only known SNP that could alter the protein structure of VDR. CYP24A1 is the gene encoding vitamin D 24 hydroxylase and is a vitamin D responsive gene. The influence of rs2228570 on transcriptional activation by VDR in human gingival fibroblasts (hGF) and periodontal ligament cells (hPDLC) was investigated in this study...
February 18, 2018: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Yu-Fang Huang, Yi-Hui Wu, Wen-Fang Cheng, Shu-Ling Peng, Wan-Lin Shen, Cheng-Yang Chou
PURPOSE: Malignant ascites of epithelial ovarian cancer (EOC) help identify prognostic biomarkers or mechanisms of tumor progression. Vitamin D-binding protein (DBP) was revealed to be upregulated in EOC ascites in our previous proteomic study. Here, we examined the role of DBP in EOC. EXPERIMENTAL DESIGN: We analyzed ascites, serum, and tissue samples of patients with newly diagnosed EOC to determine the prognostic effects of DBP. We verified DBP function using orthotopic animal models and DBP regulation in ovarian cancer cell lines...
February 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
J C Han, J G Wang, G H Chen, J L Zhang, N Zhang, H X Qu, Y Guo, Y F Yan, X J Yang
1α-Hydroxycholecalciferol (1α-OH-D3) is a vitamin D derivative. The objective of this study was to evaluate the effects of 1α-OH-D3 on the growth and the mRNA expression of vitamin D receptor (VDR) in the small intestine and kidney of chickens. A total of 240 males of one-day-old Ross 308 broilers was randomly assigned to 4 treatments with 5 replicates of 12 birds per replicate. Three levels of 1α-OH-D3 (1.25, 2.5, and 5 μg/kg) were added to a basal diet containing 0.50% calcium (Ca), 0.25% non-phytate phosphorus (NPP), and without supplemental cholecalciferol (vitamin D3)...
February 14, 2018: Poultry Science
Jiangping Song, Xiao Chen, Liang Cheng, Man Rao, Kai Chen, Ningning Zhang, Jian Meng, Mengmeng Li, Zhi-Qiang Liu, Ping-Chang Yang
Background and aims: The aberrant immune responses play a critical role in the pathogenesis of myocarditis. Vitamin D receptor (VDR) has immune regulatory functions. This study aims to investigate the role of VDR in the restricting the immune inflammation in the heart. Methods: The human heart samples were obtained from the heart transplantation. T helper (Th)2 and Th1 responses in the heart tissue were characterized by histology and immune assay. VDR-/- mice and Rag2-/- mice were used in the experiments to test the role of VDR in the maintaining the homeostasis in the heart...
February 12, 2018: Cardiovascular Research
Amitis Karrys, Islam Rady, Roxane-Cherille N Chamcheu, Marya S Sabir, Sanchita Mallick, Jean Christopher Chamcheu, Peter W Jurutka, Mark R Haussler, G Kerr Whitfield
Treatment with 1,25-dihydroxyvitamin D₃ (1,25D) improves psoriasis symptoms, possibly by inducing the expression of late cornified envelope (LCE)3 genes involved in skin repair. In psoriasis patients, the majority of whom harbor genomic deletion of LCE3B and LCE3C (LCE3C_LCE3B-del), we propose that certain dietary analogues of 1,25D activate the expression of residual LCE3A/LCE3D/LCE3E genes to compensate for the loss of LCE3B/LCE3C in the deletant genotype. Herein, human keratinocytes (HEKn) homozygous for LCE3C_LCE3B-del were treated with docosahexaenoic acid (DHA) and curcumin, two low-affinity, nutrient ligands for the vitamin D receptor (VDR)...
February 4, 2018: Nutrients
Min Wan, Xiao Tang, Rokeya Sultana Rekha, S S V Jagadeeswara Rao Muvva, Susanna Brighenti, Birgitta Agerberth, Jesper Z Haeggström
Prostaglandin (PG)E2 is an arachidonic acid-derived lipid mediator that plays an important role in inflammation and immunity. In this study, we demonstrate that PGE2 suppresses basal and 1,25-dihydroxy vitamin D3 (VD3 )-induced expression of hCAP18/LL-37 via E prostanoid (EP)2 and EP4 receptors. In humans, VD3 up-regulates vitamin D receptor (VDR) expression and promotes transcription of the cathelicidin hCAP18/LL-37 gene, whereas PGE2 counteracts this effect. We find that PGE2 induces the cAMP/PKA-signaling pathway and enhances the expression of the inhibitory transcription factor cAMP-responsive modulator/inducible cAMP early repressor, which prevents VDR expression and induction of hCAP18/LL-37 in human macrophages...
January 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Gary Loughran, Irwin Jungreis, Ioanna Tzani, Michael Power, Ruslan I Dmitriev, Ivaylo P Ivanov, Manolis Kellis, John F Atkins
Although stop codon readthrough is used extensively by viruses to expand their gene expression, verified instances of mammalian readthrough have only recently been uncovered by systems biology and comparative genomics approaches. Previously our analysis of conserved protein coding signatures that extend beyond annotated stop codons predicted stop codon readthrough of several mammalian genes, all of which have been validated experimentally. Four mRNAs display highly efficient stop codon readthrough, and these mRNAs have a UGA stop codon immediately followed by CUAG (UGA_CUAG) that is conserved throughout vertebrates...
January 31, 2018: Journal of Biological Chemistry
Anja Pemsel, Saskia Rumpf, Klaus Roemer, Kristina Heyne, Thomas Vogt, Joerg Reichrath
While nuclear cofactors that contribute to vitamin D receptor (VDR)-mediated gene transcription, including retinoid X receptors, nuclear co-activators and co-repressors, have been extensively investigated, little is known about cytoplasmic VDR-binding partners and the physiological relevance of their interaction. To gain new insight into this topic, we isolated whole-cell protein extracts of 1,25-dihydroxyvitamin D3 stimulated and UV-B-irradiated vs. non-irradiated HEK 293T cells transfected with a plasmid called pURB VDR C-Term TAP tag...
February 2018: Anticancer Research
Woo-Seok Bang, Dong-Hyun Lee, Kyoung-Tae Kim, Dae-Chul Cho, Joo-Kyung Sung, In-Bo Han, Du-Hwan Kim, Brian K Kwon, Chi Heon Kim, Ki-Su Park, Man-Kyu Park, Sung-Young Seo, Ye-Jin Seo
BACKGROUND CONTEXT: Vitamin D deficiency (VDD) has been closely linked with skeletal muscle atrophy in many studies, but to date no study has focused on paraspinal muscle. PURPOSE: To verify paraspinal muscle changes according to serum vitamin D level. STUDY DESIGN: A cross-sectional study of patients who visited our hospital and an in vivo animal study METHODS: We measured serum vitamin D concentration in 91 elderly women and stratified them according to their vitamin D status in three groups: control, vitamin D insufficiency, and VDD, and obtained magnetic resonance imaging data of the lumbar spine and evaluated the quality and quantity of the paraspinal muscles...
January 16, 2018: Spine Journal: Official Journal of the North American Spine Society
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
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
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-dihydroxyvitamin D [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-hydroxyvitamin D [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...
February 1, 2018: Endocrinology
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 (NR), 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)2 D3 ) promotes VDR binding to the nuclear matrix...
November 26, 2017: Molecular and Cellular Endocrinology
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...
March 2018: Veterinary and Comparative Oncology
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
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