miR-23b and miR-27b are pro-myogenic and are downregulated in T2DM.
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miR-23b and miR-27b regulate myogenesis through the p53 pathway.
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The p53 pathway is concordantly dysregulated in T2DM.
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.
