Dysregulation of a novel miR-23b/27b-p53 axis impairs muscle stem cell differentiation of humans with type 2 diabetes

Tora I Henriksen, Peter K Davidsen, Maria Pedersen, Heidi S Schultz, Ninna S Hansen, Therese J Larsen, Allan Vaag, Bente K Pedersen, Søren Nielsen, Camilla Scheele

    21 Citationer (Scopus)

    Abstract

    OBJECTIVE: MicroRNAs (miRNAs) are increasingly recognized as fine-tuning regulators of metabolism, and are dysregulated in several disease conditions. With their capacity to rapidly change gene expression, miRNAs are also important regulators of development and cell differentiation. In the current study, we describe an impaired myogenic capacity of muscle stem cells isolated from humans with type 2 diabetes (T2DM) and assess whether this phenotype is regulated by miRNAs.

    METHODS: We measured global miRNA expression during in vitro differentiation of muscle stem cells derived from T2DM patients and healthy controls.

    RESULTS: The mir-23b/27b cluster was downregulated in the cells of the patients, and a pro-myogenic effect of these miRNAs was mediated through the p53 pathway, which was concordantly dysregulated in the muscle cells derived from humans with T2DM.

    CONCLUSIONS: Our results indicate that we have identified a novel pathway for coordination of myogenesis, the miR-23b/27b-p53 axis that, when dysregulated, potentially contributes to a sustained muscular dysfunction in T2DM.

    OriginalsprogEngelsk
    TidsskriftMolecular Metabolism
    Vol/bind6
    Udgave nummer7
    Sider (fra-til)770-779
    Antal sider10
    ISSN2212-8778
    DOI
    StatusUdgivet - jul. 2017

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