Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1alpha
| Autor: | Johan Tisserand, Christine Dennefeld, Konstantin Khetchoumian, Pierre Chambon, Mihaela Ignat, Manuel Mark, Régine Losson, Marius Teletin |
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| Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Clinique de la Souris (ICS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Aging
030204 cardiovascular system & hematology MESH: Calcinosis Kidney Calcitriol receptor MESH: Mice Knockout MESH: Hepatocytes Mice Ectopic calcification 0302 clinical medicine Homeostasis MESH: Aging MESH: Animals MESH: Endothelial Cells Receptor Lung Mice Knockout 0303 health sciences Multidisciplinary Calcinosis Nuclear Proteins Arteries MESH: Transcription Factors Biological Sciences MESH: Gene Expression Regulation MESH: Homeostasis MESH: Calcium Signal transduction medicine.medical_specialty TRPV6 MESH: Mutation TRPV5 MESH: Receptors Calcitriol Biology 03 medical and health sciences CYP24A1 MESH: Mice Inbred C57BL Internal medicine medicine Animals MESH: Lung MESH: Mice MESH: Arteries 030304 developmental biology MESH: Vibrissae Endothelial Cells [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology MESH: Kidney medicine.disease Mice Inbred C57BL Endocrinology Gene Expression Regulation Vibrissae Mutation Hepatocytes Receptors Calcitriol Calcium MESH: Nuclear Proteins Transcription Factors Calcification |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2008, 105 (7), pp.2598-603. ⟨10.1073/pnas.0712030105⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.0712030105⟩ |
| Popis: | Calcification of arteries is a major risk factor for cardiovascular mortality in humans. Using genetic approaches, we demonstrate here that the transcriptional intermediary factor 1α (TIF1α), recently shown to function as a tumor suppressor in murine hepatocytes, also participates in a molecular cascade that prevents calcifications in arterioles and medium-sized arteries. We further provide genetic evidence that this function of TIF1α is not exerted in hepatocytes. The sites of ectopic calcifications in mutant mice lacking TIF1α resemble those seen in mice carrying an activating mutation of the calcium sensor receptor ( Casr ) gene and, in TIF1 α-deficient kidneys, Casr expression is increased together with that of many other vitamin D receptor (VDR) direct target genes, namely Car2 , Cyp24a1 , Trpv5 , Trpv6 , Calb1 , S100g , Pthlh , and Spp1 . Thus, our data indicate that TIF1α represses the VDR pathway in kidney and suggest that an up-regulation of Casr expression in this organ could account for ectopic calcifications generated upon TIF1 α deficiency. Interestingly, the calcifying arteriopathy of TIF1 α-null mutant mice shares features with the human age-related Mönckeberg's disease and, overall, the TIF1 α-null mutant pathological phenotype supports the hypothesis that aging is promoted by increased activity of the vitamin D signaling pathway. |
| Databáze: | OpenAIRE |
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