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microRNA for determining the age-related myogenic capabilities of skeletal muscle
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 fa...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Biochemistry and Molecular Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911199/ https://www.ncbi.nlm.nih.gov/pubmed/26521942 http://dx.doi.org/10.5483/BMBRep.2015.48.11.211 |
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author | Lee, Kwang-Pyo Shin, Yeo Jin Kwon, Ki-Sun |
author_facet | Lee, Kwang-Pyo Shin, Yeo Jin Kwon, Ki-Sun |
author_sort | Lee, Kwang-Pyo |
collection | PubMed |
description | 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] |
format | Online Article Text |
id | pubmed-4911199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-49111992016-06-27 microRNA for determining the age-related myogenic capabilities of skeletal muscle Lee, Kwang-Pyo Shin, Yeo Jin Kwon, Ki-Sun BMB Rep Perspective 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] Korean Society for Biochemistry and Molecular Biology 2015-11 /pmc/articles/PMC4911199/ /pubmed/26521942 http://dx.doi.org/10.5483/BMBRep.2015.48.11.211 Text en Copyright © 2015, Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/4.0/ 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. |
spellingShingle | Perspective Lee, Kwang-Pyo Shin, Yeo Jin Kwon, Ki-Sun microRNA for determining the age-related myogenic capabilities of skeletal muscle |
title | microRNA for determining the age-related myogenic capabilities of skeletal muscle |
title_full | microRNA for determining the age-related myogenic capabilities of skeletal muscle |
title_fullStr | microRNA for determining the age-related myogenic capabilities of skeletal muscle |
title_full_unstemmed | microRNA for determining the age-related myogenic capabilities of skeletal muscle |
title_short | microRNA for determining the age-related myogenic capabilities of skeletal muscle |
title_sort | microrna for determining the age-related myogenic capabilities of skeletal muscle |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911199/ https://www.ncbi.nlm.nih.gov/pubmed/26521942 http://dx.doi.org/10.5483/BMBRep.2015.48.11.211 |
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