期刊
MOLECULAR METABOLISM
卷 6, 期 7, 页码 770-779出版社
ELSEVIER
DOI: 10.1016/j.molmet.2017.04.006
关键词
Satellite cell; MicroRNA; Diabetes; Muscle; Human; Myogenesis; muscle stem cells; p53; miR-23b; miR-27b
资金
- Novo Nordisk Foundation [NNF12OC1016421]
- Faculty of Health Sciences, University of Copenhagen
- Danish Diabetes Academy
- Danish National Research Foundation [DNRF55]
- TrygFonden
- Danish Council for Strategic Research [09-067009, 09-075724]
- Danish Ministry of Science, Technology, and Innovation
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. (C) 2017 The Authors. Published by Elsevier GmbH.
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