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miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4

The myogenic capacity of myoblasts decreases in skeletal muscle with age. In addition to environmental factors, intrinsic factors are important for maintaining the regenerative potential of muscle progenitor cells, but their identities are largely unknown. Here, comparative analysis of microRNA (miR...

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Autores principales: Lee, Kwang-Pyo, Shin, Yeo Jin, Panda, Amaresh C., Abdelmohsen, Kotb, Kim, Ji Young, Lee, Seung-Min, Bahn, Young Jae, Choi, Jeong Yi, Kwon, Eun-Soo, Baek, Su-Jin, Kim, Seon-Young, Gorospe, Myriam, Kwon, Ki-Sun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536309/
https://www.ncbi.nlm.nih.gov/pubmed/26215566
http://dx.doi.org/10.1101/gad.263574.115
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author Lee, Kwang-Pyo
Shin, Yeo Jin
Panda, Amaresh C.
Abdelmohsen, Kotb
Kim, Ji Young
Lee, Seung-Min
Bahn, Young Jae
Choi, Jeong Yi
Kwon, Eun-Soo
Baek, Su-Jin
Kim, Seon-Young
Gorospe, Myriam
Kwon, Ki-Sun
author_facet Lee, Kwang-Pyo
Shin, Yeo Jin
Panda, Amaresh C.
Abdelmohsen, Kotb
Kim, Ji Young
Lee, Seung-Min
Bahn, Young Jae
Choi, Jeong Yi
Kwon, Eun-Soo
Baek, Su-Jin
Kim, Seon-Young
Gorospe, Myriam
Kwon, Ki-Sun
author_sort Lee, Kwang-Pyo
collection PubMed
description The myogenic capacity of myoblasts decreases in skeletal muscle with age. In addition to environmental factors, intrinsic factors are important for maintaining the regenerative potential of muscle progenitor cells, but their identities are largely unknown. Here, comparative analysis of microRNA (miRNA) expression profiles in young and old myoblasts uncovered miR-431 as a novel miRNA showing markedly reduced abundance in aged myoblasts. Importantly, elevating miR-431 improved the myogenic capacity of old myoblasts, while inhibiting endogenous miR-431 lowered myogenesis. Bioinformatic and biochemical analyses revealed that miR-431 directly interacted with the 3′ untranslated region (UTR) of Smad4 mRNA, which encodes one of the downstream effectors of TGF-β signaling. In keeping with the low levels of miR-431 in old myoblasts, SMAD4 levels increased in this myoblast population. Interestingly, in an in vivo model of muscle regeneration following cardiotoxin injury, ectopic miR-431 injection greatly improved muscle regeneration and reduced SMAD4 levels. Consistent with the finding that the mouse miR-431 seed sequence in the Smad4 3′ UTR is conserved in the human SMAD4 3′ UTR, inhibition of miR-431 also repressed the myogenic capacity of human skeletal myoblasts. Taken together, our results suggest that the age-associated miR-431 plays a key role in maintaining the myogenic ability of skeletal muscle with age.
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spelling pubmed-45363092016-01-31 miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4 Lee, Kwang-Pyo Shin, Yeo Jin Panda, Amaresh C. Abdelmohsen, Kotb Kim, Ji Young Lee, Seung-Min Bahn, Young Jae Choi, Jeong Yi Kwon, Eun-Soo Baek, Su-Jin Kim, Seon-Young Gorospe, Myriam Kwon, Ki-Sun Genes Dev Research Paper The myogenic capacity of myoblasts decreases in skeletal muscle with age. In addition to environmental factors, intrinsic factors are important for maintaining the regenerative potential of muscle progenitor cells, but their identities are largely unknown. Here, comparative analysis of microRNA (miRNA) expression profiles in young and old myoblasts uncovered miR-431 as a novel miRNA showing markedly reduced abundance in aged myoblasts. Importantly, elevating miR-431 improved the myogenic capacity of old myoblasts, while inhibiting endogenous miR-431 lowered myogenesis. Bioinformatic and biochemical analyses revealed that miR-431 directly interacted with the 3′ untranslated region (UTR) of Smad4 mRNA, which encodes one of the downstream effectors of TGF-β signaling. In keeping with the low levels of miR-431 in old myoblasts, SMAD4 levels increased in this myoblast population. Interestingly, in an in vivo model of muscle regeneration following cardiotoxin injury, ectopic miR-431 injection greatly improved muscle regeneration and reduced SMAD4 levels. Consistent with the finding that the mouse miR-431 seed sequence in the Smad4 3′ UTR is conserved in the human SMAD4 3′ UTR, inhibition of miR-431 also repressed the myogenic capacity of human skeletal myoblasts. Taken together, our results suggest that the age-associated miR-431 plays a key role in maintaining the myogenic ability of skeletal muscle with age. Cold Spring Harbor Laboratory Press 2015-08-01 /pmc/articles/PMC4536309/ /pubmed/26215566 http://dx.doi.org/10.1101/gad.263574.115 Text en © 2015 Lee et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Lee, Kwang-Pyo
Shin, Yeo Jin
Panda, Amaresh C.
Abdelmohsen, Kotb
Kim, Ji Young
Lee, Seung-Min
Bahn, Young Jae
Choi, Jeong Yi
Kwon, Eun-Soo
Baek, Su-Jin
Kim, Seon-Young
Gorospe, Myriam
Kwon, Ki-Sun
miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4
title miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4
title_full miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4
title_fullStr miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4
title_full_unstemmed miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4
title_short miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4
title_sort mir-431 promotes differentiation and regeneration of old skeletal muscle by targeting smad4
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536309/
https://www.ncbi.nlm.nih.gov/pubmed/26215566
http://dx.doi.org/10.1101/gad.263574.115
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