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
Autor: | Michal Majkowski, Aleksandra Marchwicka, Ewa Marcinkowska, Marian Gabryś, Łukasz Śnieżewski, Klaudia Berkowska, Sylwia Janik, Urszula Nowak, Malgorzata Cebrat, Anastasiia Satyr, Agnieszka Łaszkiewicz |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Myeloid Calcitriol receptor Mice 0302 clinical medicine polycyclic compounds Vitamin D Cells Cultured Spectroscopy blood cells vitamin D receptor retinoic acid receptors expression CYP24A1 CYP26A1 differentiation hematopoietic stem cells Cell Differentiation General Medicine Retinoic Acid 4-Hydroxylase Computer Science Applications Leukemia Myeloid Acute Haematopoiesis medicine.anatomical_structure 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Acute promyelocytic leukemia medicine.medical_specialty HL-60 Cells Tretinoin Biology Article Catalysis Inorganic Chemistry 03 medical and health sciences Promyelocytic leukemia protein Cell Line Tumor Internal medicine medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology Blood Cells Organic Chemistry medicine.disease Hematopoiesis Mice Inbred C57BL Retinoic acid receptor 030104 developmental biology Endocrinology Gene Expression Regulation Cancer research biology.protein Receptors Calcitriol |
Zdroj: | International Journal of Molecular Sciences; Volume 18; Issue 6; Pages: 1323 International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms18061323 |
Popis: | 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 VDR transcription, and unliganded RARα acts as a transcriptional repressor to VDR gene in acute myeloid leukemia (AML) cells. This is why we decided to examine the effects of the combination of 1,25D and all-trans-retinoic acid (ATRA) on VDR gene expression in normal human and murine blood cells at various steps of their development. We tested the expression of VDR 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 VDR 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 VDR. In contrast, in murine blood cells 1,25D, but not ATRA, upregulates the expression of VDR. VDR and RAR receptors are present and transcriptionally active in blood cells of both species, especially at early steps of blood development. |
Databáze: | OpenAIRE |
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