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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Jun 22

PMID 28635660

Citations 11

Authors

Sylwia Janik

Urszula Nowak

Agnieszka Laszkiewicz

Anastasiia Satyr

Michal Majkowski

Aleksandra Marchwicka

Lukasz Sniezewski

Klaudia Berkowska

Marian Gabrys

Malgorzata Cebrat

Ewa Marcinkowska

Affiliations

Soon will be listed here.

Abstract

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 transcription, and unliganded RARα acts as a transcriptional repressor to gene in acute myeloid leukemia (AML) cells. This is why we decided to examine the effects of the combination of 1,25D and all--retinoic acid (ATRA) on gene expression in normal human and murine blood cells at various steps of their development. We tested the expression of and regulation of this gene in response to 1,25D or ATRA, as well as transcriptional activities of nuclear receptors VDR and RARs in human and murine blood cells. We discovered that regulation of expression in humans is different from in mice. In human blood cells at early stages of their differentiation ATRA, but not 1,25D, upregulates the expression of . In contrast, in murine blood cells 1,25D, but not ATRA, upregulates the expression of . VDR and RAR receptors are present and transcriptionally active in blood cells of both species, especially at early steps of blood development.

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References

Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G . Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev. 2015; 96(1):365-408. PMC: 4839493. DOI: 10.1152/physrev.00014.2015. View

Byrne I, Flanagan L, Tenniswood M, Welsh J . Identification of a hormone-responsive promoter immediately upstream of exon 1c in the human vitamin D receptor gene. Endocrinology. 2000; 141(8):2829-36. DOI: 10.1210/endo.141.8.7618. View

Baker A, McDonnell D, Hughes M, Crisp T, Mangelsdorf D, Haussler M . Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U S A. 1988; 85(10):3294-8. PMC: 280195. DOI: 10.1073/pnas.85.10.3294. View

Doulatov S, Notta F, Laurenti E, Dick J . Hematopoiesis: a human perspective. Cell Stem Cell. 2012; 10(2):120-36. DOI: 10.1016/j.stem.2012.01.006. View

Zella L, Kim S, Shevde N, Pike J . Enhancers located within two introns of the vitamin D receptor gene mediate transcriptional autoregulation by 1,25-dihydroxyvitamin D3. Mol Endocrinol. 2006; 20(6):1231-47. DOI: 10.1210/me.2006-0015. View

Owusu S, Ross A . Retinoid Homeostatic Gene Expression in Liver, Lung and Kidney: Ontogeny and Response to Vitamin A-Retinoic Acid (VARA) Supplementation from Birth to Adult Age. PLoS One. 2016; 11(1):e0145924. PMC: 4701161. DOI: 10.1371/journal.pone.0145924. View

Gocek E, Kielbinski M, Wylob P, Kutner A, Marcinkowska E . Side-chain modified vitamin D analogs induce rapid accumulation of VDR in the cell nuclei proportionately to their differentiation-inducing potential. Steroids. 2008; 73(14):1359-66. DOI: 10.1016/j.steroids.2008.06.010. View

Baurska H, Kielbinski M, Biecek P, Haus O, Jazwiec B, Kutner A . Monocytic differentiation induced by side-chain modified analogs of vitamin D in ex vivo cells from patients with acute myeloid leukemia. Leuk Res. 2014; 38(5):638-47. DOI: 10.1016/j.leukres.2014.03.009. View

Bouillon R, Bischoff-Ferrari H, Willett W . Vitamin D and health: perspectives from mice and man. J Bone Miner Res. 2008; 23(7):974-9. DOI: 10.1359/jbmr.080420. View

10.

Rhinn M, Dolle P . Retinoic acid signalling during development. Development. 2012; 139(5):843-58. DOI: 10.1242/dev.065938. View

11.

Halsall J, Osborne J, Hutchinson P, Pringle J . In silico analysis of the 5' region of the Vitamin D receptor gene: functional implications of evolutionary conservation. J Steroid Biochem Mol Biol. 2007; 103(3-5):352-6. DOI: 10.1016/j.jsbmb.2006.12.046. View

12.

Aranda A, Pascual A . Nuclear hormone receptors and gene expression. Physiol Rev. 2001; 81(3):1269-304. DOI: 10.1152/physrev.2001.81.3.1269. View

13.

Canete A, Cano E, Munoz-Chapuli R, Carmona R . Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis. Nutrients. 2017; 9(2). PMC: 5331590. DOI: 10.3390/nu9020159. View

14.

Ma Y, Trump D, Johnson C . Vitamin D in combination cancer treatment. J Cancer. 2010; 1:101-7. PMC: 2938072. DOI: 10.7150/jca.1.101. View

15.

Laszkiewicz A, Cebrat M, Miazek A, Kisielow P . Complexity of transcriptional regulation within the Rag locus: identification of a second Nwc promoter region within the Rag2 intron. Immunogenetics. 2011; 63(3):183-7. PMC: 3035778. DOI: 10.1007/s00251-011-0511-2. View

16.

Tenen D . Disruption of differentiation in human cancer: AML shows the way. Nat Rev Cancer. 2003; 3(2):89-101. DOI: 10.1038/nrc989. View

17.

Cortes M, Chen M, Stachura D, Liu S, Kwan W, Wright F . Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production. Cell Rep. 2016; 17(2):458-468. PMC: 5338633. DOI: 10.1016/j.celrep.2016.09.012. View

18.

Kahlen J, Carlberg C . Identification of a vitamin D receptor homodimer-type response element in the rat calcitriol 24-hydroxylase gene promoter. Biochem Biophys Res Commun. 1994; 202(3):1366-72. DOI: 10.1006/bbrc.1994.2081. View

19.

Pan P, Reddy K, Lee S, Studzinski G . Differentiation-related regulation of 1,25-dihydroxyvitamin D3 receptor mRNA in human leukaemia cells HL-60. Cell Prolif. 1991; 24(2):159-70. DOI: 10.1111/j.1365-2184.1991.tb01146.x. View

20.

Thatcher J, Isoherranen N . The role of CYP26 enzymes in retinoic acid clearance. Expert Opin Drug Metab Toxicol. 2009; 5(8):875-86. PMC: 2730205. DOI: 10.1517/17425250903032681. View