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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...

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Autores principales: Lee, Kwang-Pyo, Shin, Yeo Jin, Kwon, Ki-Sun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2015
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]
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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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