{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390282679407553408.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.5551/jat.20818"}},{"identifier":{"@type":"COI","@value":"1:STN:280:DC%2BC2czmslCqtQ%3D%3D"}},{"identifier":{"@type":"PMID","@value":"24441913"}},{"identifier":{"@type":"URI","@value":"https://www.jstage.jst.go.jp/article/jat/21/5/21_20818/_pdf"}},{"identifier":{"@type":"NAID","@value":"130004444733"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/2015033743"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@language":"en","@value":"5-aza-2´-Deoxycytidine, a DNA Methyltransferase Inhibitor, Facilitates the Inorganic Phosphorus-Induced Mineralization of Vascular Smooth Muscle Cells"}],"dc:language":"en","description":[{"type":"abstract","notation":[{"@language":"en","@value":"<b><i>Aim</i></b>: Vascular calcification, an independent risk factor for cardiovascular disease in patients with chronic kidney disease(CKD), refers to the mineralization of vascular smooth muscle cells(VSMCs) caused by phenotypic changes toward osteoblast-like cells. DNA methylation, mediated by DNA methyltransferases(DNMTs), plays an important role in the differentiation of osteoblasts. We herein assessed the effects of a DNMT inhibitor on phenotypic changes in VSMCs and the development of vascular calcification.<br>\r\n<b><i>Methods</i></b>: The effects of 5-aza´-2-deoxycytidine(5-aza-dC), a DNMT inhibitor, on human aortic smooth muscle cells(HASMCs) were evaluated. The expression and DNA methylation status of osteogenic genes were determined using RT-qPCR and bisulfite sequencing, respectively. Mineralization of HASMCs was induced by high concentrations of inorganic phosphate(Pi), as confirmed by quantitation of the calcium levels and von Kossa staining. Moreover, we examined the effects of the suppression of DNMT1 and/or alkaline phosphatase(ALP) on the mineralization of HASMCs.<br>\r\n<b><i>Results</i></b>: 5-aza-dC increased the expression and activity of ALP and reduced the DNA methylation levels of the ALP promoter region in the HASMCs. In addition, both treatment with 5-aza-dC and downregulation of the DNMT1 expression promoted the Pi-induced mineralization of HASMCs. Moreover, both treatment with phosphonoformic acid(PFA), a sodium-dependent phosphate transporter inhibitor, and suppression of the ALP expression inhibited the 5-aza-dC-promoted mineralization of HASMCs.<br>\r\n<b><i>Conclusions</i></b>: The present study showed that DNMT inhibitors facilitate the Pi-induced development of vascular calcification via the upregulation of the ALP expression along with a reduction in the DNA methylation level of the ALP promoter region."}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420282801205631744","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10824782"},{"@type":"NRID","@value":"1000010824782"},{"@type":"NRID","@value":"9000257812297"},{"@type":"NRID","@value":"9000283344726"},{"@type":"NRID","@value":"9000408656411"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/ikimonodaisuki12"}],"foaf:name":[{"@language":"en","@value":"Azechi Takuya"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326228515968","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10468580"},{"@type":"NRID","@value":"1000010468580"},{"@type":"NRID","@value":"9000367429526"},{"@type":"NRID","@value":"9000257808169"},{"@type":"NRID","@value":"9000005811636"},{"@type":"NRID","@value":"9000277876282"},{"@type":"NRID","@value":"9000005793164"},{"@type":"NRID","@value":"9000257812298"},{"@type":"NRID","@value":"9000411202865"},{"@type":"NRID","@value":"9000257808051"},{"@type":"NRID","@value":"9000283344731"},{"@type":"NRID","@value":"9000243877215"},{"@type":"NRID","@value":"9000021206836"},{"@type":"NRID","@value":"9000257807067"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/hinataiju"}],"foaf:name":[{"@language":"en","@value":"Sato Fumiaki"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679407553410","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257812299"}],"foaf:name":[{"@language":"en","@value":"Sudo Ryo"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences"}]},{"@id":"https://cir.nii.ac.jp/crid/1410282679407553409","@type":"Researcher","personIdentifier":[{"@type":"NRID","@value":"9000257812300"}],"foaf:name":[{"@language":"en","@value":"Wachi Hiroshi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"13403478"},{"@type":"EISSN","@value":"18803873"}],"prism:publicationName":[{"@language":"en","@value":"Journal of Atherosclerosis and Thrombosis"},{"@language":"ja","@value":"Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ"},{"@language":"en","@value":"JAT"},{"@language":"en","@value":"J Atheroscler Thromb"},{"@language":"ja","@value":"Ｊ　Ａｔｈｅｒｏｓｃｌｅｒ　Ｔｈｒｏｍｂ"}],"dc:publisher":[{"@language":"en","@value":"Japan Atherosclerosis Society"},{"@language":"ja","@value":"一般社団法人 日本動脈硬化学会"}],"prism:publicationDate":"2014","prism:volume":"21","prism:number":"5","prism:startingPage":"463","prism:endingPage":"476"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://www.jstage.jst.go.jp/article/jat/21/5/21_20818/_pdf"},{"@id":"https://search.jamas.or.jp/link/ui/2015033743"}],"availableAt":"2014","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Vascular%20calcification","dc:title":"Vascular calcification"},{"@id":"https://cir.nii.ac.jp/all?q=Vascular%20smooth%20muscle%20cells","dc:title":"Vascular smooth muscle cells"},{"@id":"https://cir.nii.ac.jp/all?q=Alkaline%20phosphatase","dc:title":"Alkaline phosphatase"},{"@id":"https://cir.nii.ac.jp/all?q=5-aza-2%C2%B4-deoxycytidine","dc:title":"5-aza-2´-deoxycytidine"},{"@id":"https://cir.nii.ac.jp/all?q=DNA%20methylation","dc:title":"DNA methylation"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011144130988800","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Phosphate feeding induces arterial medial calcification in uremic mice: role of serum phosphorus, fibroblast growth factor-23, and osteopontin"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011144893152768","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Epigenetic studies of genomic retroelements in major psychosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145375547648","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"RETRACTED: 5-Aza-Deoxycytidine Induces Selective Degradation of DNA Methyltransferase 1 by a Proteasomal Pathway That Requires the KEN Box, Bromo-Adjacent Homology Domain, and Nuclear Localization Signal"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145490235136","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Aging, DNA methylation and cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011146550529280","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Elastin Degradation and Vascular Smooth Muscle Cell Phenotype Change Precede Cell Loss and Arterial Medial Calcification in a Uremic Mouse Model of Chronic Kidney Disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292618949180544","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Vascular calcification and cardiovascular function in chronic kidney disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292620075834496","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The fundamental role of epigenetic events in cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292620188880000","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574092893929088","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"DNA methylation patterns and epigenetic memory"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094089829248","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094182182912","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"GADD45A Protein Plays an Essential Role in Active DNA Demethylation during Terminal Osteogenic Differentiation of Adipose-derived Mesenchymal Stem Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095898011008","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Coronary-Artery Calcification in Young Adults with End-Stage Renal Disease Who Are Undergoing Dialysis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574096372240768","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Calcium, phosphate and parathyroid metabolism in kidney transplanted patients"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569285314048","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"DNA methylation in animal development"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855571505624320","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Epigenetic modifications in cardiovascular 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Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895880108288","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825896239470464","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Vascular Calcification"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825896407935232","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"5-Azacytidine facilitates osteogenic gene expression and differentiation of mesenchymal stem cells by alteration in DNA methylation"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107369550638208","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Targeting of 5-aza-2′-deoxycytidine residues by chromatin-associated DNMT1 induces proteasomal degradation of the free enzyme"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107370169312768","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Phosphate and vascular calcification: Emerging role of the sodium-dependent phosphate co-transporter PiT-1"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107371370175744","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845409725312","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Arterial Calcification in Chronic Kidney Disease: Key Roles for Calcium and Phosphate"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845632756096","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Biocompatibility of xenogeneic bone, commercially available coral, 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Muscle Cell Proliferation via Induction of p21WAF1"}]},{"@id":"https://cir.nii.ac.jp/crid/2051433317027164928","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mechanism of phosphate-induced calcification in rat aortic tissue culture : possible involvement of Pit-1 and apoptosis"}]}],"dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:1003544742"},{"@type":"CROSSREF","@value":"10.5551/jat.20818"},{"@type":"PUBMED","@value":"24441913"},{"@type":"CIA","@value":"130004444733"},{"@type":"OPENAIRE","@value":"doi_dedup___::ead687613d1a95aadd0bda62527ea53a"},{"@type":"CROSSREF","@value":"10.5551/jat.28647_references_DOI_4cJUPXrIV4ShGL8S7LnacHB7Hk8"}]}