Vitamin D receptor signaling mechanisms: Integrated actions of a well-defined transcription factor

Carlberg, Carsten; Campbell, Moray J.

doi:10.1016/j.steroids.2012.10.019

Cited by 238 publications

(197 citation statements)

References 109 publications

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“…Members of this superfamily are expressed in virtually all cell types and are highly integrated functionally. [2][3][4][5] These receptors represent some of the most successful examples of targeted therapies [6][7][8][9] and, more widely, in human disease they represent the target for approximately 15% of all drugs (reviewed in 10,11 ). Of the family of 48 NRs, at least 30 are expressed in the prostate 2 and many are well established in the etiology of prostate cancer (CaP), for example, the androgen receptor (AR) (reviewed in 12 ), VDR (reviewed in 9 ), and the peroxisome proliferator-activated receptors (PPARs) (reviewed in 6 ).…”

Section: Introductionmentioning

confidence: 99%

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription

et al. 2015

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The Vitamin D Receptor (VDR) is a member of the nuclear receptor superfamily and is of therapeutic interest in cancer and other settings. Regulation of microRNA (miRNA) by the VDR appears to be important to mediate its actions, for example, to control cell growth. To identify if and to what extent VDR-regulated miRNA patterns change in prostate cancer progression, we undertook miRNA microarray analyses in 7 cell models representing non-malignant and malignant prostate cells (RWPE-1, RWPE-2, HPr1, HPr1AR, LNCaP, LNCaP-C4-2, and PC-3). To focus on primary VDR regulatory events, we undertook expression analyses after 30 minutes treatment with 1a,25(OH) 2 D 3 . Across all models, 111 miRNAs were significantly modulated by 1a,25(OH) 2 D 3 treatment. Of these, only 5 miRNAs were modulated in more than one cell model, and of these, only 3 miRNAs were modulated in the same direction. The patterns of miRNA regulation, and the networks they targeted, significantly distinguished the different cell types. Integration of 1a,25 (OH) 2 D 3 -regulated miRNAs with published VDR ChIP-seq data showed significant enrichment of VDR peaks in flanking regions of miRNAs. Furthermore, mRNA and miRNA expression analyses in non-malignant RWPE-1 cells revealed patterns of miRNA and mRNA co-regulation; specifically, 13 significant reciprocal patterns were identified and these patterns were also observed in TCGA prostate cancer data. Lastly, motif search analysis revealed differential motif enrichment within VDR peaks flanking mRNA compared to miRNA genes. Together, this study revealed that miRNAs are rapidly regulated in a highly cell-type specific manner, and are significantly co-integrated with mRNA regulation.

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Section: Introductionmentioning

confidence: 99%

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription

et al. 2015

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“…The VDR gene is distributed on chromosome 12q12-q14. Eight exons and six alternatively spliced regions (1a-1f) are located in functionally relevant areas, including the promoter region [23], [26].…”

Section: Resultsmentioning

confidence: 99%

“…Genes that have the sequence Different considered polymorphic. [23], [26] Polymorphisms are formed through a process of mutation that can occur because of the substitution, deletions or insertions in the polynucleotide sequence. Polymorphisms have a neutral effect on biological function.…”

Section: Resultsmentioning

confidence: 99%

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Association Vitamin D Receptor (TaqI) Gene Polymorphism with Anthropometric Parameters and Blood Pressure of College Students in Faculty of Medicine, University of Sumatera Utara

Sari¹

2017

Proceedings of the 1st Public Health International Conference (PHICo 2016)

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Abstract-Epidemiological studies suggest several genes from the vitamin D receptor have been implicated in obesity and cardiovascular disease. However, the findings were inconsistent.The aim of this study was to evaluate TaqI polymorphism of the vitamin D receptor (VDR) gene are associated with anthropometric parameters and blood pressure on college students in Faculty of Medicine, Sumatera Utara University.This was a cross-sectional study. Measurements of anthropometric parameters were carried out. Blood pressure measurement using a mercury sphygmomanometer. TaqI polymorphiss of VDR gene were geno-typed by PCR and FRLP. Statistical analysis were calculated using SPPS software (version 14.0).The prevalence of TaqI genotypes were 117 (84%) TT and 22 (16%) Tt. Homozygous tt was not found in the subjects. There were no significant differences in anthropometric parameters (BMI and WHR) and blood pressure between TaqI polymorphism of the VDR gene (p=0.321; p=0.607; p=0.278)The results suggest that TaqI VDR polymorphism are not related with the obesity and not risk factor of cardiovascular disease on college students in

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“…The biologically active metabolite of vitamin D 3 , 1α,25-dihydroxyvitamin D 3 (1,25D3), is a steroid hormone with high affinity for the intracellular/nuclear vitamin D receptor (VDR) [1].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D3 modulates the innate immune response through regulation of the hCAP-18/LL-37 gene expression and cytokine production

2015

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The steroid hormone metabolite of vitamin D 3 , 1α,25-dihydroxyvitamin D 3 (1,25D3), promotes osteogenic activity and regulates calcium and phosphate metabolism, which are actions regarded as classical vitamin D-regulated functions. Besides its role in these processes, 1,25D3 also seems implicated in the host defense against microbial/proinflammatory attacks. Low serum levels of vitamin D 3 (vitamin D deficiency) are associated with osteoporosis and increased risk of fractures but also inflammatory diseases and their disease progression, presumably via mechanisms associated with 1,25D3-evoked modulation of the innate immune system. 1,25D3 has been reported to modulate many inflammatory responses, suggesting that it regulates multiple transcriptional targets within the inflammatory system. Experimental studies in various experimental systems show that 1,25D3 differentially regulates the production of pro-inflammatory cytokines and chemokines depending on cell type. Importantly, many reports show that 1,25D3 up-regulates expression of the human antimicrobial peptide hCAP-18/LL-37 gene. The hCAP-18/LL-37 gene seems indeed to be an important transcriptional target for 1,25D3. However, only weak evidence is presented showing that 1,25D3 consistently increases the amount of biologically active LL-37 peptide.In the present review, we discuss 1,25D3-induced down-regulation of cytokine/chemokine production and stimulation of hCAP-18/LL-37 gene expression which represent two very important pathways for 1,25D3-evoked regulation of the innate immune response.

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Vitamin D receptor signaling mechanisms: Integrated actions of a well-defined transcription factor

Cited by 238 publications

References 109 publications

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription

Association Vitamin D Receptor (TaqI) Gene Polymorphism with Anthropometric Parameters and Blood Pressure of College Students in Faculty of Medicine, University of Sumatera Utara

Vitamin D3 modulates the innate immune response through regulation of the hCAP-18/LL-37 gene expression and cytokine production

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