title: miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy.
abstract: 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-binding homeobox, transforming growth factor-β1, 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada Medical Research Center, Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, People's Republic of China.
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.affiliation: Medical Research Center, Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, People's Republic of China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
authors.forename: Shali
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
authors.forename: Xuran
authors.initials: X
authors.lastname: Chu
authors.affiliation: Medical Research Center, Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, People's Republic of China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada subrata.chakrabarti@schulich.uwo.ca.
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D004452:Echocardiography; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D005947:Glucose