title: Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes.
abstract: Diabetic cardiomyopathy is a cascade of complex events leading to eventual failure of the heart and cardiac fibrosis being considered as one of its major causes. miR-133a is one of the most abundantly expressed microRNAs in the heart. We investigated the role of miR-133a during severe hyperglycaemia. And, our aim was to find out what role miR-133a plays during diabetes-induced cardiac fibrosis. We saw a drastic decrease in miR-133a expression in the hearts of streptozotocin-induced diabetic animals, as measured by RT-qPCR. This decrease was accompanied by an increase in the transcriptional co-activator EP300 mRNA and major markers of fibrosis [transforming growth factor-β1, connective tissue growth factor, fibronectin (FN1) and COL4A1]; in addition, focal cardiac fibrosis assessed by Masson's trichome stain was increased. Interestingly, in diabetic mice with cardiac-specific miR-133aa overexpression, cardiac fibrosis was significantly decreased, as observed by RT-qPCR and immunoblotting of COL4A1, ELISA for FN1 and microscopic examination. Furthermore, Cardiac miR-133a overexpression prevented ERK1/2 and SMAD-2 phosphorylation. These findings show that miR-133a could be a potential therapeutic target for diabetes-induced cardiac fibrosis and related cardiac dysfunction.
authors.affiliation: Department of Pathology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
authors.forename: Shali
authors.initials: S
authors.lastname: Chen
authors.forename: Prasanth
authors.initials: P
authors.lastname: Puthanveetil
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.forename: Scot J
authors.initials: SJ
authors.lastname: Matkovich
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Dorn
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology*; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D012333:RNA, Messenger; D000808:Angiotensinogen; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse
keywords: cardiac fibrosis; diabetes; miRNA 133