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The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy
Muscle wasting, also known as cachexia, is associated with many chronic diseases, which worsens prognosis of primary illness leading to enhanced mortality. Molecular basis of this metabolic syndrome is not yet completely understood. SIRT6 is a chromatin-bound member of the sirtuin family, implicated...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605688/ https://www.ncbi.nlm.nih.gov/pubmed/28928419 http://dx.doi.org/10.1038/s41598-017-10838-5 |
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author | Samant, Sadhana A. Kanwal, Abhinav Pillai, Vinodkumar B. Bao, Riyue Gupta, Mahesh P. |
author_facet | Samant, Sadhana A. Kanwal, Abhinav Pillai, Vinodkumar B. Bao, Riyue Gupta, Mahesh P. |
author_sort | Samant, Sadhana A. |
collection | PubMed |
description | Muscle wasting, also known as cachexia, is associated with many chronic diseases, which worsens prognosis of primary illness leading to enhanced mortality. Molecular basis of this metabolic syndrome is not yet completely understood. SIRT6 is a chromatin-bound member of the sirtuin family, implicated in regulating many cellular processes, ranging from metabolism, DNA repair to aging. SIRT6 knockout (SIRT6-KO) mice display loss of muscle, fat and bone density, typical characteristics of cachexia. Here we report that SIRT6 depletion in cardiac as well as skeletal muscle cells promotes myostatin (Mstn) expression. We also observed upregulation of other factors implicated in muscle atrophy, such as angiotensin-II, activin and Acvr2b, in SIRT6 depleted cells. SIRT6-KO mice showed degenerated skeletal muscle phenotype with significant fibrosis, an effect consistent with increased levels of Mstn. Additionally, we observed that in an in vivo model of cancer cachexia, Mstn expression coupled with downregulation of SIRT6. Furthermore, SIRT6 overexpression downregulated the cytokine (TNFα-IFNγ)-induced Mstn expression in C2C12 cells, and promoted myogenesis. From the ChIP assay, we found that SIRT6 controls Mstn expression by attenuating NF-κB binding to the Mstn promoter. Together, these data suggest a novel role for SIRT6 in maintaining muscle mass by controlling expression of atrophic factors like Mstn and activin. |
format | Online Article Text |
id | pubmed-5605688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56056882017-09-20 The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy Samant, Sadhana A. Kanwal, Abhinav Pillai, Vinodkumar B. Bao, Riyue Gupta, Mahesh P. Sci Rep Article Muscle wasting, also known as cachexia, is associated with many chronic diseases, which worsens prognosis of primary illness leading to enhanced mortality. Molecular basis of this metabolic syndrome is not yet completely understood. SIRT6 is a chromatin-bound member of the sirtuin family, implicated in regulating many cellular processes, ranging from metabolism, DNA repair to aging. SIRT6 knockout (SIRT6-KO) mice display loss of muscle, fat and bone density, typical characteristics of cachexia. Here we report that SIRT6 depletion in cardiac as well as skeletal muscle cells promotes myostatin (Mstn) expression. We also observed upregulation of other factors implicated in muscle atrophy, such as angiotensin-II, activin and Acvr2b, in SIRT6 depleted cells. SIRT6-KO mice showed degenerated skeletal muscle phenotype with significant fibrosis, an effect consistent with increased levels of Mstn. Additionally, we observed that in an in vivo model of cancer cachexia, Mstn expression coupled with downregulation of SIRT6. Furthermore, SIRT6 overexpression downregulated the cytokine (TNFα-IFNγ)-induced Mstn expression in C2C12 cells, and promoted myogenesis. From the ChIP assay, we found that SIRT6 controls Mstn expression by attenuating NF-κB binding to the Mstn promoter. Together, these data suggest a novel role for SIRT6 in maintaining muscle mass by controlling expression of atrophic factors like Mstn and activin. Nature Publishing Group UK 2017-09-19 /pmc/articles/PMC5605688/ /pubmed/28928419 http://dx.doi.org/10.1038/s41598-017-10838-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Samant, Sadhana A. Kanwal, Abhinav Pillai, Vinodkumar B. Bao, Riyue Gupta, Mahesh P. The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy |
title | The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy |
title_full | The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy |
title_fullStr | The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy |
title_full_unstemmed | The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy |
title_short | The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy |
title_sort | histone deacetylase sirt6 blocks myostatin expression and development of muscle atrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605688/ https://www.ncbi.nlm.nih.gov/pubmed/28928419 http://dx.doi.org/10.1038/s41598-017-10838-5 |
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