Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post-translational modifications

Ženata, Ondřej; Vrzal, Radim

doi:10.18632/oncotarget.15697

Cited by 54 publications

(47 citation statements)

References 106 publications

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“…However, the difference in VDR protein levels detected in the present study between samples of the same patient, excludes genetics or changes in serum VD levels as responsible for the VDR down-regulation observed in cells coming from damaged tissues. Of interest, this reduced VDR protein expression parallels with no changes in VDR mRNA expression at the same time point and remains stable over several passages, which strongly suggests the epigenetic regulation of VDR by local inflammation or damage associated to CD [29]. In this line, the overexpression of both miR-125b [30] and miR27b [31], which were shown to be differentially regulated by CD [32], were associated with reduced VDR protein levels.…”

Section: Discussionmentioning

confidence: 67%

Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D

et al. 2020

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Vitamin D (VD) deficiency has been associated to Crohn’s disease (CD) pathogenesis, and the exogenous administration of VD improves the course of the disease, but the mechanistic basis of these observations remains unknown. Vitamin D receptor (VDR) mediates most of the biological functions of this hormone, and we aim to analyze here the expression of VDR in intestinal tissue, epithelial cells, and fibroblasts from CD patients. The effects of VD on a fibroblast wound healing assay and murine intestinal fibrosis are also analyzed. Our data show diminished VDR protein levels in surgical resections and epithelial cells from CD patients. In intestinal fibroblasts isolated from damaged tissue of CD patients, we detected enhanced migration and decreased VDR expression compared with both fibroblasts from non-damaged tissue of the same CD patient or control fibroblasts. Treatment with VD increased VDR protein levels, avoided the accelerated migration in CD fibroblasts, and prevented murine intestinal fibrosis induced by the heterotopic transplant model. In conclusion, our study demonstrates diminished VDR protein levels associated with enhanced migration in intestinal fibroblasts from damaged tissue of CD patients. In these cells, VD accumulates VDR and normalizes migration, which supports that CD patients would benefit from the VD anti-fibrotic therapeutic value that we demonstrate in a murine experimental model.

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Section: Discussionmentioning

confidence: 67%

Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D

et al. 2020

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“…Bioinformatic analysis of the miRNA-mRNA-lncRNA interaction network identified 16 core genes, including 6 mRNAs (Vdr, Mgp, Fabp3, Fst, Cd38, and Col1a1), 5 miRNAs (miR-483, miR-298, miR-361, miR-92b and miR-155), and 5 lncRNAs (NR_046246.1, NR_046239.1, XR_086062.1, XR_145872.1 and XR_146737.1). Vdr, a ligand-activated transcription factor, has been reported to be a core gene during MSC osteogenic differentiation [ 5 , 6 , 50 ], and matrix gla protein (Mgp) has been recognized as a potent calcification inhibitor and regulator of bone morphogenetic protein-2 (BMP-2) [ 51 ]. Wang et al [ 52 ] indicated that overexpression of fatty acid binding protein 3 (Fabp3) inhibited MSC growth and proliferation via negatively regulating the cell cycle and MSC growth factors and enhancing cell survival under hypoxic or ischaemic conditions, which indicated that the Fabp3 gene potentially promotes MSC osteogenic differentiation.…”

Section: Discussionmentioning

confidence: 99%

Profiling the miRNA-mRNA-lncRNA interaction network in MSC osteoblast differentiation induced by (+)-cholesten-3-one

et al. 2018

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BackgroundOur previous study showed that (+)-cholesten-3-one (CN) has the potential to induce the osteoblastic differentiation of mesenchymal stem cells (MSCs). However, the roles of CN in targeting miRNA-mRNA-lncRNA interactions to regulate osteoblast differentiation remain poorly understood.ResultsA total of 77 miRNAs (36 upregulated and 41 downregulated) and 295 lncRNAs (281 upregulated and 14 downregulated) were significantly differentially expressed during CN-induced MSC osteogenic differentiation. Bioinformatic analysis identified that several pathways may play vital roles in MSC osteogenic differentiation, such as the vitamin D receptor signalling, TNF signalling, PI3K-Akt signalling, calcium signalling, and mineral absorption pathways. Further bioinformatic analysis revealed 16 core genes, including 6 mRNAs (Vdr, Mgp, Fabp3, Fst, Cd38, and Col1a1), 5 miRNAs (miR-483, miR-298, miR-361, miR-92b and miR-155) and 5 lncRNAs (NR_046246.1, NR_046239.1, XR_086062.1, XR_145872.1 and XR_146737.1), that may play important roles in regulating the CN-induced osteogenic differentiation of MSCs. Verified by the luciferase reporter, AR-S, qRT-PCR and western blot assays, we identified one miRNA (miR-298) that may enhance the osteogenic differentiation potential of MSCs via the vitamin D receptor signalling pathway.ConclusionsThis study revealed the global expression profile of miRNAs and lncRNAs involved in the Chinese medicine active ingredient CN-induced osteoblast differentiation of MSCs for the first time and provided a foundation for future investigations of miRNA-mRNA-lncRNA interaction networks to completely illuminate the regulatory role of CN in MSC osteoblast differentiation.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5155-2) contains supplementary material, which is available to authorized users.

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“…Vitamin D Receptor (VDR) protein, a member of the nuclear receptor superfamily of ligand-activated transcription factors, is thought to be implicated in several cell biological events (e.g., calcium and phosphate homeostasis, cell differentiation and apoptosis) [1,2]. The human VDR gene is mapped on chromosome 12 and contains four common polymorphisms, namely rs7975232 A/C in intron eight (ApaI) rs1544410 G/A in intron eight (BsmI), rs2228570 T/ C in exon two (FokI), and rs731236 T/C in exon nine (TaqI) [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Pooling analysis regarding the impact of human vitamin D receptor variants on the odds of psoriasis

Sun

et al. 2019

BMC Med Genet

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Background The study aims at scientifically investigating the genetic effect of four polymorphisms (rs7975232, rs1544410, rs2228570, and rs731236) within the human Vitamin D Receptor (VDR) gene on the odds of psoriasis through an updated meta-analysis. Methods We searched eight databases and screened the studies for pooling. Finally, a total of eighteen eligible case-control studies were included. BH (Benjamini & Hochberg) adjusted P-values of association (Passociation) and odd ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated under the allele, homozygote, heterozygote, dominant, recessive, and carrier models. Results Compared with the negative controls, no statistically significant difference in the odds of psoriasis was detected for the cases under any genetic models (BH adjusted Passociation > 0.05). We also performed subgroup meta-analyses by the source of controls, ethnicity, country, Hardy-Weinberg equilibrium, and genotyping method. Similar results were observed in most subgroup meta-analyses (BH adjusted Passociation > 0.05). Besides, data of Begg’s and Egger’s tests excluded the significant publication bias; while the sensitivity analysis data further indicated the statistical reliability of our pooling results. Conclusion The currently available data fails to support a robust association between VDR rs7975232, rs1544410, rs2228570 and rs731236 polymorphisms and psoriasis susceptibility, which still required the support of more case-control studies.

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Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post-translational modifications

Cited by 54 publications

References 106 publications

Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D

Diminished Vitamin D Receptor Protein Levels in Crohn’s Disease Fibroblasts: Effects of Vitamin D

Profiling the miRNA-mRNA-lncRNA interaction network in MSC osteoblast differentiation induced by (+)-cholesten-3-one

Pooling analysis regarding the impact of human vitamin D receptor variants on the odds of psoriasis

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