title: MicroRNA-494 plays a role in fiber type-specific skeletal myogenesis in human induced pluripotent stem cells.
abstract: Mitochondrial oxidative capacity in skeletal muscle is known to decrease in diabetic patients, and sarcopenia is a risk factor for diabetes, particularly in elderly people. We previously revealed that microRNA (miR)-494 inhibits mitochondrial biogenesis during myogenic differentiation in murine C2C12 cells and others reported that exercise regulates miR-494 levels in obese sedentary individuals with increased risk of type 2 diabetes. In this study, to investigate the therapeutic potential of miR-494, we first investigated the role of miR-494 during human skeletal myogenesis. Using human induced pluripotent stem (hiPS) cells stably transfected with the Tet/ON-myogenic differentiation 1(MYOD1) gene (MyoD-hiPS cells), we found that miR-494 expression transiently increased and was downregulated after myogenic induction. In miR-494 transfected MyoD-hiPS cells, the level of high oxidative fiber (type IIa) marker proteins specifically decreased, while no change in the total number of cells was observed. In contrast, the expression of both type I and type IIx markers was unaffected by miR-494 overexpression. Furthermore, miR-494 overexpression suppressed basal oxygen consumption rate concomitant with the inhibition of myotube formation and without significant effects on the mitochondrial content. These results suggest that miR-494 plays a novel role in the fiber type-specific skeletal myogenesis in MyoD-hiPS cells, distinct from murine C2C12 myogenesis.
authors.affiliation: Division of Pharmacology, Department of Medicine, Shiga University of Medical Science, Japan; Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwasaki
authors.affiliation: Division of Pharmacology, Department of Medicine, Shiga University of Medical Science, Japan. Electronic address: timamura@belle.shiga-med.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Katsutaro
authors.initials: K
authors.lastname: Morino
authors.affiliation: Division of Pharmacology, Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimosato
authors.affiliation: Division of Pharmacology, Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tawa
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ugi
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.affiliation: Division of Pharmacology, Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Okamura
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C547168:MIRN494 microRNA, human; D035683:MicroRNAs
keywords: Human skeletal myogenesis; Induced pluripotent stem cell; Myosin heavy chain; miR-494