The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy

Sadhana A. Samant, Abhinav Kanwal, Vinodkumar B. Pillai, Riyue Bao, Mahesh P. Gupta

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number11877
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 01-12-2017

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Myostatin
Histone Deacetylases
Muscular Atrophy
Cachexia
Activins
Knockout Mice
Muscles
Skeletal Muscle
Down-Regulation
Muscle Development
Angiotensin II
DNA Repair
Bone Density
Muscle Cells
Chromatin
Myocardium
Fibrosis
Chronic Disease
Up-Regulation
Fats

All Science Journal Classification (ASJC) codes

  • General

Cite this

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. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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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.

In: Scientific Reports, Vol. 7, No. 1, 11877, 01.12.2017.

Research output: Contribution to journalArticle

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