Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1038/s41598-019-41476-8 http://hdl.handle.net/11449/185581 |
Resumo: | We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for similar to 22 months following Dicer inactivation to determine if myomiR expression would be further reduced over a prolonged timeframe and assess the effects of myomiR depletion on skeletal muscle phenotype. Skeletal muscle Dicer mRNA expression remained significantly decreased by 80% in old KO mice and sequencing of cloned Dicer mRNA revealed the complete absence of the floxed exons in KO skeletal muscle. Despite a further reduction of myomiR expression to similar to 50% ofWT, no change was observed in muscle morphology between WT and KO groups. These results indicate the life-long reduction in myomiR levels did not adversely affect skeletal muscle phenotype and suggest the possibility that microRNA expression is uniquely regulated in skeletal muscle. |
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spelling |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphologyWe generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for similar to 22 months following Dicer inactivation to determine if myomiR expression would be further reduced over a prolonged timeframe and assess the effects of myomiR depletion on skeletal muscle phenotype. Skeletal muscle Dicer mRNA expression remained significantly decreased by 80% in old KO mice and sequencing of cloned Dicer mRNA revealed the complete absence of the floxed exons in KO skeletal muscle. Despite a further reduction of myomiR expression to similar to 50% ofWT, no change was observed in muscle morphology between WT and KO groups. These results indicate the life-long reduction in myomiR levels did not adversely affect skeletal muscle phenotype and suggest the possibility that microRNA expression is uniquely regulated in skeletal muscle.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)NIHUniv Kentucky, Coll Med, Dept Physiol, Lexington, KY 40506 USAColl Hlth Sci, Dept Rehabil Sci, Lexington, KY USAUniv Kentucky, Ctr Muscle Biol, Lexington, KY 40506 USASao Paulo State Univ, Inst Biosci, Dept Morphol, Botucatu, SP, BrazilOrebro Univ, Sch Hlth Sci, Orebro, SwedenSao Paulo State Univ, Inst Biosci, Dept Morphol, Botucatu, SP, BrazilFAPESP: 2014/24327-1FAPESP: 2015/19193-9NIH: AR061939NIH: AR071753Nature Publishing GroupUniv KentuckyColl Hlth SciUniversidade Estadual Paulista (Unesp)Orebro UnivVechetti, Ivan J. [UNESP]Wen, YuanChaillou, ThomasMurach, Kevin A.Alimov, Alexander P.Figueiredo, Vandre C.Dal-Pai-Silva, Maeli [UNESP]McCarthy, John J.2019-10-04T12:36:45Z2019-10-04T12:36:45Z2019-04-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11http://dx.doi.org/10.1038/s41598-019-41476-8Scientific Reports. London: Nature Publishing Group, v. 9, 11 p., 2019.2045-2322http://hdl.handle.net/11449/18558110.1038/s41598-019-41476-8WOS:000462990000025Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScientific Reportsinfo:eu-repo/semantics/openAccess2021-10-23T20:17:37Zoai:repositorio.unesp.br:11449/185581Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-05-23T20:15:43.175556Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology |
title |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology |
spellingShingle |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology Vechetti, Ivan J. [UNESP] |
title_short |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology |
title_full |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology |
title_fullStr |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology |
title_full_unstemmed |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology |
title_sort |
Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology |
author |
Vechetti, Ivan J. [UNESP] |
author_facet |
Vechetti, Ivan J. [UNESP] Wen, Yuan Chaillou, Thomas Murach, Kevin A. Alimov, Alexander P. Figueiredo, Vandre C. Dal-Pai-Silva, Maeli [UNESP] McCarthy, John J. |
author_role |
author |
author2 |
Wen, Yuan Chaillou, Thomas Murach, Kevin A. Alimov, Alexander P. Figueiredo, Vandre C. Dal-Pai-Silva, Maeli [UNESP] McCarthy, John J. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Univ Kentucky Coll Hlth Sci Universidade Estadual Paulista (Unesp) Orebro Univ |
dc.contributor.author.fl_str_mv |
Vechetti, Ivan J. [UNESP] Wen, Yuan Chaillou, Thomas Murach, Kevin A. Alimov, Alexander P. Figueiredo, Vandre C. Dal-Pai-Silva, Maeli [UNESP] McCarthy, John J. |
description |
We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for similar to 22 months following Dicer inactivation to determine if myomiR expression would be further reduced over a prolonged timeframe and assess the effects of myomiR depletion on skeletal muscle phenotype. Skeletal muscle Dicer mRNA expression remained significantly decreased by 80% in old KO mice and sequencing of cloned Dicer mRNA revealed the complete absence of the floxed exons in KO skeletal muscle. Despite a further reduction of myomiR expression to similar to 50% ofWT, no change was observed in muscle morphology between WT and KO groups. These results indicate the life-long reduction in myomiR levels did not adversely affect skeletal muscle phenotype and suggest the possibility that microRNA expression is uniquely regulated in skeletal muscle. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-04T12:36:45Z 2019-10-04T12:36:45Z 2019-04-02 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1038/s41598-019-41476-8 Scientific Reports. London: Nature Publishing Group, v. 9, 11 p., 2019. 2045-2322 http://hdl.handle.net/11449/185581 10.1038/s41598-019-41476-8 WOS:000462990000025 |
url |
http://dx.doi.org/10.1038/s41598-019-41476-8 http://hdl.handle.net/11449/185581 |
identifier_str_mv |
Scientific Reports. London: Nature Publishing Group, v. 9, 11 p., 2019. 2045-2322 10.1038/s41598-019-41476-8 WOS:000462990000025 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Scientific Reports |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
11 |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1803045658974748672 |