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VDR AND transcription

Yong-Sik Bong, Shahin Assefnia, Therese Tuohy, Deborah W Neklason, Randall W Burt, Jaeil Ahn, Hao-Wen J Jiang, Stephen W Byers
Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity. We treated VDR null mice with the carcinogen azoxymethane (AOM) and generated mice bearing a mutated APC (hypomorph) on a VDR null background (Apc1638N/+Vdr-/-)...
October 19, 2016: Oncotarget
Kristine C Olson, Paige M Kulling, Thomas L Olson, Su-Fern Tan, Rebecca J Rainbow, David J Feith, Thomas P Loughran
Large granular lymphocyte leukemia (LGLL) is a rare incurable chronic disease typically characterized by clonal expansion of CD3+ cytotoxic T-cells. Two signal transducer and activator of transcription factors, STAT1 and STAT3, are constitutively active in T-LGLL. Disruption of this activation induces apoptosis in T-LGLL cells. Therefore, considerable efforts are focused on developing treatments that inhibit STAT activation. Calcitriol, the active form of vitamin D, has been shown to decrease STAT1 and STAT3 phosphorylation in cancer cell lines and autoimmune disease mouse models...
October 7, 2016: Cancer Biology & Therapy
Zujaja-Tul-Noor Hamid Mehmood, Dimitrios Papandreou
Vitamin D related research continues to expand and theorise regarding its involvement in obesity, as both hypovitaminosis D and obesity strike in pandemic proportions. Vitamin D plays an important role in immune system through Vitamin D Receptors (VDR), which are transcription factors located abundantly in the body. Due to this characteristic, it is potentially linked to obesity, which is a state of inflammation involving the release of cytokines from adipose tissue, and exerting stress on other organs in a state of positive energy balance...
September 15, 2016: Open Access Macedonian Journal of Medical Sciences
Mei-Hua Bao, Huai-Qing Luo, Li-Hua Chen, Liang Tang, Kui-Fen Ma, Ju Xiang, Li-Ping Dong, Jie Zeng, Guang-Yi Li, Jian-Ming Li
Atherosclerosis is a chronic multifactorial inflammatory disease with high prevalence worldwide, and has become the leading cause of death. The present study was designed to investigate the impact of high-fat diet on ApoE(-/-) mice exhibiting atherosclerosis by detecting the genome-wide expression profile of lncRNAs and mRNAs. A total of 354 differentially expressed lncRNAs were identified (≥2.0 folds). Simultaneously, 357 differentially expressed mRNAs from the same chip were found. The expression differences of lncRNAs and mRNAs were consistent in both qPCR and microarray detection...
October 4, 2016: Scientific Reports
Fatouma Alimirah, Xinjian Peng, Akash Gupta, Liang Yuan, JoEllen Welsh, Michele Cleary, Rajendra G Mehta
The vitamin D receptor (VDR), and its ligand 1α,25-dihydroxyvitamin D3 (1,25D3) prevent breast cancer development and progression, yet the molecular mechanisms governing this are unclear. MicroRNAs (miRNAs) on the other hand, promote or inhibit breast cancer growth. To understand how VDR regulates miRNAs, we compared miRNA expression of wild-type (WT) and VDR knockout (VDRKO) breast cancer cells by a Mouse Breast Cancer miRNA PCR array. Compared to VDR WT cells, expressions of miR-214, miR-199a-3p and miR-199a-5p of the miR-199a/miR-214 cluster were 42, 15, and 10 fold higher in VDRKO cells respectively...
September 27, 2016: Experimental Cell Research
Anna Y Belorusova, Nanjoo Suh, Hong Jin Lee, Jae Young So, Hubert Maehr, Natacha Rochel
Gemini analogs of calcitriol, characterized by the extension of the C21-methyl group of calcitriol with a second chain, act as agonists of the vitamin D receptor (VDR). This second side chain of gemini is accommodated in a new cavity inside the VDR created by the structural rearrangement of the protein core. The resulting conformational change preserves the active state of the receptor and bestows gemini compounds with biological activities that exceed those of calcitriol. Of particular interest are gemini's anti-cancer properties, and in this study we demonstrate anti-proliferative and tumor-reducing abilities of BXL0124 and BXL0097, differing only by the presence or absence, respectively, of the methylene group on the A ring...
September 17, 2016: Journal of Steroid Biochemistry and Molecular Biology
Sara Azarpeykan, Keren E Dittmer, Jonathan C Marshall, Kalyani C Perera, Erica K Gee, Els Acke, Keith G Thompson
The aim of this study was to determine the relative abundance and relationship of vitamin D responsive and calcium transporting transcripts (TRPV5, TRPV6, calD9k, calD28k, PMCA, NCX1, CYP27B1, CYP24A1, and VDR) in ovine, canine and, equine kidney using quantitative real-time PCR (RT-qPCR), and then perform a comparison between the three species. Renal tissue samples were harvested post-mortem from 10 horses, 10 sheep, and five dogs. Primers were designed for each gene. For each sample total RNA was extracted, cDNA synthesised, and RT-qPCR was performed...
2016: PloS One
Jenna M Christensen, Jasmine Cheng, Peter Earls, Jenny Gunton, William Sewell, Raymond Sacks, Richard J Harvey
BACKGROUND: Vitamin D deficiency is associated with many inflammatory respiratory disease states. However, serum vitamin D concentrations may not reflect tissue-specific availability. In this study we sought to assess the local expression of genes essential in vitamin D regulation in chronic rhinosinusitis (CRS). METHODS: A cross-sectional study of adult patients undergoing endoscopic sinus surgery was performed. Patients were defined as having CRS with polyps (CRSwNP) or without polyps (CRSsNP), or normal sinus mucosa...
September 12, 2016: International Forum of Allergy & Rhinology
Dapeng Jin, Yong-Guo Zhang, Shaoping Wu, Rong Lu, Zhijie Lin, Yuanyuan Zheng, Honglei Chen, Gabriella Cs-Szabo, Jun Sun
BACKGROUND: Axin1 is a scaffold protein in the β-catenin destruction complex, which, if disrupted, contributes to pathogenesis of various human diseases, including colorectal carcinogenesis and inflammatory bowel diseases (IBD). We have previously demonstrated that Salmonella infection promotes the degradation and plasma sequestration of Axin1, leading to bacterial invasiveness and inflammatory responses. Vitamin D and the vitamin D receptor (VDR) appear to be important regulators of IBD and colon cancer...
September 4, 2016: Journal of Steroid Biochemistry and Molecular Biology
Marcin Szybinski, Katarzyna Sokolowska, Rafal R Sicinski, Lori A Plum, Hector F DeLuca
Prompted by results of molecular modeling performed on the seco-d-ring-vitamins D, we turned our attention to such analogs, having reversed configurations at C-13 and C-14, as the next goals of our studies on the structure-activity relationship for vitamin D compounds. First, we developed an efficient total synthesis of the "upper" C/seco-d-ring fragment with a 7-carbon side chain. Then, we coupled it with A-ring fragments using Sonogashira or Wittig-Horner protocol, providing the targeted D-seco analogs of 1α,25-dihydroxyvitamin D3 and 1α,25-dihydroxy-19-norvitamin D3 possessing a vinyl substituent at C-14 and a double bond between C-17 and C-20...
August 26, 2016: Journal of Steroid Biochemistry and Molecular Biology
Olivia B Yu, Leggy A Arnold
Calcitroic acid was isolated and characterized almost four decades ago, but little is known about this important vitamin D metabolite. Four reported synthetic strategies to generate calcitroic acid are presented that highlight the scientific progress in the field of chemistry directed to vitamin D analog synthesis. The most recent synthesis described the generation of calcitroic acid with an overall yield of 12.8% in 13 steps. The endogenous formation of calcitroic acid has been demonstrated in perfused rat kidney using 24,25,26,27-tetranor-1,23(OH)2D3...
October 21, 2016: ACS Chemical Biology
Antonio Neme, Sabine Seuter, Carsten Carlberg
CCCTC-binding factor (CTCF) is a transcription factor being involved in 3D chromatin organization and displays a highly conserved genome-wide binding pattern. In this study, we report the cistrome of CTCF in THP-1 human monocytes and confirm that from the 40,078 CTCF binding sites nearly 85% are identical with those found in K562 monocytes. Quadruplicate chromatin immunoprecipitation sequencing (ChIP-seq) demonstrated that at 2130 loci the association strenght of CTCF with genomic DNA was significantly (p<0...
August 25, 2016: Biochimica et Biophysica Acta
Yong-Feng Hou, Si-Hai Gao, Ping Wang, He-Mei Zhang, Li-Zhi Liu, Meng-Xuan Ye, Guang-Ming Zhou, Zeng-Li Zhang, Bing-Yan Li
Ovarian cancer is the most lethal gynecological malignancy due to its high metastatic ability. Epithelial-mesenchymal transition (EMT) is essential during both follicular rupture and epithelium regeneration. However, it may also accelerate the progression of ovarian carcinomas. Experimental studies have found that 1α,25-dihydroxyvitamin-D3 [1α,25(OH)₂D₃] can inhibit the proliferation of ovarian cancer cells. In this study, we investigated whether 1α,25(OH)₂D₃ could inhibit the migration of ovarian cancer cells via regulating EMT...
2016: International Journal of Molecular Sciences
Jill E Larsen, Vaishnavi Nathan, Jihan K Osborne, Rebecca K Farrow, Dhruba Deb, James P Sullivan, Patrick D Dospoy, Alexander Augustyn, Suzie K Hight, Mitsuo Sato, Luc Girard, Carmen Behrens, Ignacio I Wistuba, Adi F Gazdar, Nicholas K Hayward, John D Minna
Increased expression of zinc finger E-box binding homeobox 1 (ZEB1) is associated with tumor grade and metastasis in lung cancer, likely due to its role as a transcription factor in epithelial-to-mesenchymal transition (EMT). Here, we modeled malignant transformation in human bronchial epithelial cells (HBECs) and determined that EMT and ZEB1 expression are early, critical events in lung cancer pathogenesis. Specific oncogenic mutations in TP53 and KRAS were required for HBECs to engage EMT machinery in response to microenvironmental (serum/TGF-β) or oncogenetic (MYC) factors...
September 1, 2016: Journal of Clinical Investigation
Xiaoliang Wang, Hongwei Wang, Bing Shen, Brian R Overholser, Bruce R Cooper, Yinghao Lu, Huamei Tang, Chongzhi Zhou, Xing Sun, Lin Zhong, Murray J Favus, Brian S Decker, Wanqing Liu, Zhihai Peng
Mycophenolic acid (MPA) is an important immunosuppressant broadly used in renal transplantation. However, the large inter-patient variability in mycophenolic acid (MPA) pharmacokinetics (PK) limits its use. We hypothesize that extrahepatic metabolism of MPA may have significant impact on MPA PK variability. Two intestinal UDP-glucuronosyltransferases 1A8 and 1A10 plays critical role in MPA metabolism. Both in silico and previous genome-wide analyses suggested that vitamin D (VD) may regulate intestinal UGT1A expression...
July 19, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Yue Fan, Kumi Futawaka, Rie Koyama, Yuki Fukuda, Misa Hayashi, Miyuki Imamoto, Takashi Miyawaki, Masato Kasahara, Tetsuya Tagami, Kenji Moriyama
BACKGROUND: The impact of vitamin D3 (VD3) on obesity has been reported in the past. Our study was aimed at investigating the possible mechanisms by which VD3 affects obesity induced by a high fat diet. METHODS: Eight-week-old C57BL/6 J male mice were fed a normal- or high-fat diet for 9 weeks and were treated with a gavage of vehicle (corn oil) or cholecalciferol (50 μg/kg, daily). Body weight, white adipose tissue weight, blood lipid and glucose levels were measured...
2016: Journal of Biomedical Science
Feifei Sun, Yangchun Cao, Chao Yu, Xiaoshi Wei, Junhu Yao
BACKGROUND: Calcium is a vital mineral and an indispensable component of milk for ruminants. The regulation of transcellular calcium transport by 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3, the active form of vitamin D) has been confirmed in humans and rodents, and regulators, including vitamin D receptor (VDR), calcium binding protein D9k (calbindin-D9k), plasma membrane Ca(2+)-ATPase 1b (PMCA1b), PMAC2b and Orai1, are involved in this process. However, it is still unclear whether 1,25-(OH)2D3 could stimulate calcium transport in the ruminant mammary gland...
2016: Journal of Animal Science and Biotechnology
Daniel D Bikle, Yan Jiang, Thai Nguyen, Yuko Oda, Chia-Ling Tu
1,25 dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D, and calcium regulate epidermal differentiation. 1,25(OH)2D exerts its effects through the vitamin D receptor (VDR), a transcription factor in the nuclear hormone receptor family, whereas calcium acts through the calcium sensing receptor (Casr), a membrane bound member of the G protein coupled receptor family. We have developed mouse models in which the Vdr and Casr have been deleted in the epidermis ((epid) Vdr (-∕-) and (epid) Casr (-∕-))...
2016: Frontiers in Physiology
Miguel A Maestro, Ferdinand Molnár, Antonio Mouriño, Carsten Carlberg
INTRODUCTION: Vitamin D3 activates via its hormonal form 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), the transcription factor vitamin D receptor (VDR). VDR is expressed in most human tissues and has more than 1,000 target genes. Thus, 1α,25(OH)2D3 and its synthetic analogs have a broad physiological impact. The crystal structures of the VDR ligand-binding domain (LBD), and its various ligands, further the understanding of the receptor's molecular actions. AREAS COVERED: We discuss the most important novel VDR ligands and the further insight derived from new structural information on VDR...
July 25, 2016: Expert Opinion on Therapeutic Patents
Jörg Reichrath, Christos C Zouboulis, Thomas Vogt, Michael F Holick
Vitamin D represents one of the major driving factors for the development of life on earth and for human evolution. While up to 10-20 % of the human organism's requirements in vitamin D can be obtained by the diet (under most living conditions in the USA and Europe), approximately 90 % of all needed vitamin D has to be photosynthesized in the skin through the action of the sun (ultraviolet-B (UV-B)). The skin represents a key organ of the human body's vitamin D endocrine system (VDES), being both the site of vitamin D synthesis and a target tissue for biologically active vitamin D metabolites...
July 22, 2016: Reviews in Endocrine & Metabolic Disorders
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