title: miR-150 regulates high glucose-induced cardiomyocyte hypertrophy by targeting the transcriptional co-activator p300.
abstract: p300, a transcriptional co-activator with histone acetyl transferase (HAT) activity, plays an essential role in the pathogenesis of cardiomyocyte hypertrophy in response to multiple pro-hypertrophic stimuli including hyperglycemia. However, the precise mechanisms by which p300 expression is regulated remain unclear. The purpose of this study was to investigate the role of miR-150, a potential p300-targeting microRNA (miRNA), in the post-transcriptional control of p300 expression and cardiomyocyte hypertrophy induced by high glucose. We observed that the expression of miR-150 was significantly reduced, whereas the expression of p300 was strongly elevated, concomitant with cardiomyocyte hypertrophy, in the hearts of diabetic rats compared with normal controls. Similar alterations were observed in neonatal rat cardiomyocytes that had been exposed to high levels of glucose. miR-150 mimics inhibited p300 3'-UTR luciferase reporter activity, as well as endogenous p300 expression. In addition, miR-150 mimics prevented glucose-induced cardiomyocyte hypertrophy. Co-transfection with a p300 expression vector and miR-150 mimics reversed the protective effect of miR-150 on cardiomyocyte hypertrophy. We further showed that the high glucose-mediated activation of PKCβ(2) in turn mediated the down-regulation of miR-150 expression. These data demonstrated a novel upstream role for miR-150 in p300-mediated cardiomyocyte hypertrophy and revealed a previously uncharacterized miRNAs and HATs cross-talk mechanism for the hypertrophic phenotype induced by high glucose.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Duan
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Su
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Du
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D006984:Hypertrophy / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D050881:E1A-Associated p300 Protein; D005947:Glucose; D035683:MicroRNAs; C533097:MIR150, human