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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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