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microRNA for determining the age-related myogenic capabilities of skeletal muscle
microRNA for determining the age-related myogenic capabilities of skeletal muscle
BMB Reports. 2015. Nov, 48(11): 595-596
Copyright © 2015, Korean Society for Biochemistry and Molecular Biology
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • Received : October 16, 2015
  • Published : November 30, 2015
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About the Authors
Kwang-Pyo, Lee
Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141
Yeo Jin, Shin
Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea
Ki-Sun, Kwon
Department of Functional Genomics, Korea University of Science and Technology, Daejeon 34113, Korea
kwonks@kribb.re.kr

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. [BMB Reports 2015; 48(11): 595-596]
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Acknowledgements
This work was supported by grants from the Bio & Medical Technology Development Program (20110030133 and 2013M3A9B6076413, K.-S.K.) of the National Research Foundation (NRF), which is funded by the Ministry of Science, ICT & Future Planning (MSIP), and the KRIBB Research Initiative Program.
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