MicroRNA-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiac myocytes.
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.
Horie
Takahiro
T
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Ono
Koh
K
Nishi
Hitoo
H
Iwanaga
Yoshitaka
Y
Nagao
Kazuya
K
Kinoshita
Minako
M
Kuwabara
Yasuhide
Y
Takanabe
Rieko
R
Hasegawa
Koji
K
Kita
Toru
T
Kimura
Takeshi
T
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
D051275:Glucose Transporter Type 4; C520013:Klf15 protein, rat; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; C495694:Slc2a4 protein, rat