microRNA for determining the age-related myogenic capabilities of skeletal muscle = 노화에 따른 근육분화능 조절 microRNA

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Title
microRNA for determining the age-related myogenic capabilities of skeletal muscle = 노화에 따른 근육분화능 조절 microRNA
Author(s)
Kwang-Pyo Lee; Yeo-Jin Shin; Ki Sun Kwon
Bibliographic Citation
BMB Reports, vol. 48, no. 11, pp. 595-596
Publication Year
2015
Abstract
Skeletal muscle exhibits a loss of muscle mass and function with age. Decreased regenerative potential of muscle stem/ progenitor cells is a major underlying cause of sarcopenia. We analyzed microRNAs (miRNA) that are differentially expressed in young and old myoblasts, to identify novel intrinsic factors that play a degenerative role in aged skeletal muscle. miR-431, one of decreasing miRNAs in old myoblasts, improved the myogenic differentiation when overexpressed in old myoblast, but suppressed their myogenic capability in knockdowned young myoblasts. We found that miR-431 directly binds to 3' untranslated regions (UTR) of Smad4 mRNA, and decreases its expression. Given that SMAD4 is one of the downstream effectors of TGF-β, a well-known degenerative signaling pathway in myogenesis, the decreased miR-431 in old myoblast causes SMAD4 elevation, thus resulting in defective myogenesis. Exogenous expression of miR-431 greatly improved the muscle regeneration in the cardiotoxin-injured hindlimb muscle of old mice by reducing SMAD4 levels. Since the miR-431 seed sequence is conserved in human SMAD4 3'UTR, miR-431 regulates the myogenic capacity of human skeletal myoblasts in the same manner. Our results suggest that age-associated miR-431 is required for the maintenance of the myogenic capability in myoblasts, thus underscoring its potential as a therapeutic target to slow down muscle aging.
Keyword
DifferentiationmiR-431Muscle agingMyoblastSMAD4
ISSN
1225-8687
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.5483/BMBRep.2015.48.11.211
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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