title: MicroRNA-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiac myocytes.
abstract: GLUT4 shows decreased levels in failing human adult hearts. We speculated that GLUT4 expression in cardiac muscle may be fine-tuned by microRNAs. Forced expression of miR-133 decreased GLUT4 expression and reduced insulin-mediated glucose uptake in cardiomyocytes. A computational miRNA target prediction algorithm showed that KLF15 is one of the targets of miR-133. It was confirmed that over-expression of miR-133 reduced the protein level of KLF15, which reduced the level of the downstream target GLUT4. Cardiac myocytes infected with lenti-decoy, in which the 3'UTR with tandem sequences complementary to miR-133 was linked to the luciferase reporter gene, had decreased miR-133 levels and increased levels of GLUT4. The expression levels of KLF15 and GLUT4 were decreased at the left ventricular hypertrophy and congestive heart failure stage in a rat model. The present results indicated that miR-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiomyocytes.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Horie
authors.forename: Koh
authors.initials: K
authors.lastname: Ono
authors.forename: Hitoo
authors.initials: H
authors.lastname: Nishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagao
authors.forename: Minako
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: Rieko
authors.initials: R
authors.lastname: Takanabe
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D020303:Rats, Inbred Dahl
chemical_list: D051275:Glucose Transporter Type 4; C520013:Klf15 protein, rat; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; C495694:Slc2a4 protein, rat