{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:26:27Z","timestamp":1788819987070,"version":"build-2803163510"},"reference-count":31,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":246,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"name":"Heart and Stroke Foundation of Ontario"},{"DOI":"10.13039\/100007476","name":"Canadian Diabetes Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007476","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:p>Hyperglycemia-induced endothelial injury is a key pathogenetic factor in diabetic cardiomyopathy. Endothelial injury may lead to a phenotypic change (i.e., endothelial-to-mesenchymal transition [EndMT]), causing cardiac fibrosis. Epigenetic mechanisms, through specific microRNA, may regulate such a process. We investigated the mechanisms for such changes in cardiac microvascular endothelial cells and in the heart of genetically engineered mice with chemically induced diabetes. Cardiac tissues and isolated mouse heart endothelial cells (MHECs) from animals with or without endothelial-specific overexpression of miR-200b, with or without streptozotocin-induced diabetes, were examined at the mRNA and protein levels for endothelial and mesenchymal markers. Expression of miR-200b and its targets was quantified. Cardiac functions and structures were analyzed. In the hearts of wild-type diabetic mice, EndMT was observed, which was prevented in the miR-200b transgenic diabetic mice. Expression of specific markers such as vascular endothelial growth factor, zinc finger E-box\u2013binding homeobox, transforming growth factor-\u03b21, and p300 were increased in the hearts of diabetic mice and were prevented following miR-200b overexpression. MHECs showed similar changes. miR-200b overexpression also prevented diabetes-induced cardiac functional and structural changes. These data indicate that glucose-induced EndMT in vivo and in vitro in the hearts of diabetic mice is possibly mediated by miR-200b and p300.<\/jats:p>","DOI":"10.2337\/db15-1033","type":"journal-article","created":{"date-parts":[[2015,12,31]],"date-time":"2015-12-31T03:43:57Z","timestamp":1451533437000},"page":"768-779","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":114,"title":["miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy"],"prefix":"10.2337","volume":"65","author":[{"given":"Biao","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"},{"name":"Medical Research Center, Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Cao","sequence":"additional","affiliation":[{"name":"Medical Research Center, Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shali","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuran","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Chu","sequence":"additional","affiliation":[{"name":"Medical Research Center, Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subrata","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2015,12,30]]},"reference":[{"key":"2022031300481274500_B1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/00019501-199602000-00001","article-title":"Diabetic cardiomyopathy: an overview","volume":"7","author":"LeWinter","year":"1996","journal-title":"Coron Artery Dis"},{"key":"2022031300481274500_B2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/clc.4960180604","article-title":"Cardiac consequences of diabetes mellitus","volume":"18","author":"Shehadeh","year":"1995","journal-title":"Clin Cardiol"},{"key":"2022031300481274500_B3","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1006\/jmcc.2000.1197","article-title":"Diabetes-induced myocardial structural changes: role of endothelin-1 and its receptors","volume":"32","author":"Chen","year":"2000","journal-title":"J Mol Cell Cardiol"},{"key":"2022031300481274500_B4","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/dmrr.322","article-title":"Contributions of endothelin-1 and sodium hydrogen exchanger-1 in the diabetic myocardium","volume":"18","author":"Hileeto","year":"2002","journal-title":"Diabetes Metab Res Rev"},{"key":"2022031300481274500_B5","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.cellsig.2011.12.024","article-title":"Molecular basis of cardiac endothelial-to-mesenchymal transition (EndMT): differential expression of microRNAs during EndMT","volume":"24","author":"Ghosh","year":"2012","journal-title":"Cell Signal"},{"key":"2022031300481274500_B6"},{"key":"2022031300481274500_B7","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/nm1613","article-title":"Endothelial-to-mesenchymal transition contributes to cardiac fibrosis","volume":"13","author":"Zeisberg","year":"2007","journal-title":"Nat Med"},{"key":"2022031300481274500_B8","doi-asserted-by":"crossref","first-page":"7321","DOI":"10.1167\/iovs.14-15167","article-title":"Mechanisms of endothelial to mesenchymal transition in the retina in diabetes","volume":"55","author":"Cao","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022031300481274500_B9","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1161\/CIRCULATIONAHA.110.938217","article-title":"Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts through stimulation of endothelial-to-mesenchymal transition","volume":"121","author":"Widyantoro","year":"2010","journal-title":"Circulation"},{"key":"2022031300481274500_B10","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.2337\/db06-0519","article-title":"Diabetes-induced extracellular matrix protein expression is mediated by transcription coactivator p300","volume":"55","author":"Kaur","year":"2006","journal-title":"Diabetes"},{"key":"2022031300481274500_B11","doi-asserted-by":"crossref","first-page":"24R","DOI":"10.1203\/pdr.0b013e3180457684","article-title":"Epigenetics and microRNAs","volume":"61","author":"Chuang","year":"2007","journal-title":"Pediatr Res"},{"key":"2022031300481274500_B12"},{"key":"2022031300481274500_B13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.lfs.2013.12.199","article-title":"miRNA-1 regulates endothelin-1 in diabetes","volume":"98","author":"Feng","year":"2014","journal-title":"Life Sci"},{"key":"2022031300481274500_B14","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.2337\/db11-0478","article-title":"miR-146a-Mediated extracellular matrix protein production in chronic diabetes complications","volume":"60","author":"Feng","year":"2011","journal-title":"Diabetes"},{"key":"2022031300481274500_B15","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.2337\/db10-1557","article-title":"MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy","volume":"60","author":"McArthur","year":"2011","journal-title":"Diabetes"},{"key":"2022031300481274500_B16","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/jcmm.12218","article-title":"Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes","volume":"18","author":"Chen","year":"2014","journal-title":"J Cell Mol Med"},{"key":"2022031300481274500_B17"},{"key":"2022031300481274500_B18","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1242\/dev.121.4.1089","article-title":"Vascular endothelial cell lineage-specific promoter in transgenic mice","volume":"121","author":"Schlaeger","year":"1995","journal-title":"Development"},{"key":"2022031300481274500_B19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0022-1759(00)00258-1","article-title":"Isolation of endothelial cells from murine tissue","volume":"244","author":"Marelli-Berg","year":"2000","journal-title":"J Immunol Methods"},{"key":"2022031300481274500_B20","doi-asserted-by":"crossref","first-page":"S285","DOI":"10.2337\/dc11-s239","article-title":"Endothelial dysfunction in diabetes: the role of reparatory mechanisms","volume":"34","author":"Avogaro","year":"2011","journal-title":"Diabetes Care"},{"key":"2022031300481274500_B21","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: a unifying mechanism","volume":"54","author":"Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"2022031300481274500_B22","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: small RNAs with a big role in gene regulation","volume":"5","author":"He","year":"2004","journal-title":"Nat Rev Genet"},{"key":"2022031300481274500_B23","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.2353\/ajpath.2009.090096","article-title":"Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice","volume":"175","author":"Li","year":"2009","journal-title":"Am J Pathol"},{"key":"2022031300481274500_B24","doi-asserted-by":"crossref","first-page":"e001770","DOI":"10.1161\/JAHA.115.001770","article-title":"Endothelial p53 deletion improves angiogenesis and prevents cardiac fibrosis and heart failure induced by pressure overload in mice","volume":"4","author":"Gogiraju","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"2022031300481274500_B25","doi-asserted-by":"crossref","first-page":"E127","DOI":"10.1152\/ajpendo.00432.2009","article-title":"Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells","volume":"298","author":"Chen","year":"2010","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031300481274500_B26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/01.RES.77.1.1","article-title":"Molecular regulation of atrioventricular valvuloseptal morphogenesis","volume":"77","author":"Eisenberg","year":"1995","journal-title":"Circ Res"},{"key":"2022031300481274500_B27","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/1755-1536-5-S1-S7","article-title":"Molecular mechanisms of endothelial to mesenchymal cell transition (EndoMT) in experimentally induced fibrotic diseases","volume":"5","author":"Piera-Velazquez","year":"2012","journal-title":"Fibrogenesis Tissue Repair"},{"key":"2022031300481274500_B28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2009.09.026","article-title":"Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis","volume":"48","author":"Liu","year":"2010","journal-title":"Free Radic Biol Med"},{"key":"2022031300481274500_B29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1139\/cjpp-2012-0251","article-title":"Oxidative-stress-induced epigenetic changes in chronic diabetic complications","volume":"91","author":"Feng","year":"2013","journal-title":"Can J Physiol Pharmacol"},{"key":"2022031300481274500_B30","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.pharmthera.2005.10.008","article-title":"Vascular endothelial dysfunction in diabetic cardiomyopathy: pathogenesis and potential treatment targets","volume":"111","author":"Farhangkhoee","year":"2006","journal-title":"Pharmacol Ther"},{"key":"2022031300481274500_B31","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/jcp.21162","article-title":"The transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis","volume":"213","author":"Ghosh","year":"2007","journal-title":"J Cell Physiol"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/diabetes.diabetesjournals.org\/syndication\/doi\/10.2337\/db15-1033","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/65\/3\/768\/582264\/db151033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/65\/3\/768\/582264\/db151033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:48:09Z","timestamp":1667407689000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/65\/3\/768\/35049\/miR-200b-Mediates-Endothelial-to-Mesenchymal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,30]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,12,30]]},"published-print":{"date-parts":[[2016,3,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db15-1033","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,30]]}}}