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Cited by 31Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchHistone Deacetylase Inhibitors Research

Reduced HDAC2 in Skeletal Muscle of COPD Patients

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To, Masako, Swallow, Elisabeth B., Akashi, Kenich, Haruki, Kosuke, Natanek, S Amanda, Polkey, Michael I., Ito, Kazuhiro, Barnes, Peter J.·2017·Respiratory Research
DOI 10.1186/s12931-017-0588-8PMC PMC5438490
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Abstract

Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) is an important predictor of poor prognosis, but the molecular mechanisms of muscle weakness in COPD have not been fully elucidated. The aim of this study was to investigate the role of histone deacetylases(HDAC) in skeletal muscle weakness in COPD. Twelve COPD patients, 8 smokers without COPD (SM) and 4 healthy non-smokers (NS) were recruited to the study. HDAC2 protein expression in quadriceps muscle biopsies of COPD patients (HDAC2/β-actin: 0.59 ± 0.34) was significantly lower than that in SM (1.9 ± 1.1, p = 0.0007) and NS (1.2 ± 0.7, p = 0.029). HDAC2 protein in skeletal muscle was significantly correlated with forced expiratory volume in 1 s % predicted (FEV 1 % pred) (r s = 0.53, p = 0.008) and quadriceps maximum voluntary contraction force (MVC) (r s = 0.42, p = 0.029). HDAC5 protein in muscle biopsies of COPD patients (HDAC5/β-actin: 0.44 ± 0.26) was also significantly lower than that in SM (1.29 ± 0.39, p = 0.0001) and NS (0.98 ± 0.43, p = 0.020). HDAC5 protein in muscle was significantly correlated with FEV 1 % pred (r s = 0.64, p = 0.0007) but not with MVC (r s = 0.30, p = 0.180). Nuclear factor-kappa B (NF-κB) DNA binding activity in muscle biopsies of COPD patients (10.1 ± 7.4) was significantly higher than that in SM (3.9 ± 7.3, p = 0.020) and NS (1.0 ± 1.2, p = 0.004and significantly correlated with HDAC2 decrease (r s = −0.59, p = 0.003) and HDAC5 (r s = 0.050, p = 0.012). HDAC2 knockdown by RNA interference in primary skeletal muscle cells caused an increase in NF-κB activity, NF-κB acetylation and basal tumour necrosis factor (TNF)-α production, as well as progressive cell death through apoptosis. Skeletal muscle weakness in COPD may result from HDAC2 down-regulation in skeletal muscle via acetylation and activation of NF-κB. The restoration of HDAC2 levels might be a therapeutic target for improving skeletal muscle weakness in COPD.

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  • Downregulation of HDAC2 by RNA interference in cultured primary myotubes increased TNF-α production and cell apoptosis.

    “a recent study has found that the downregulation of histone deacetylase 2 (HDAC2) by RNA interference in cultured primary myotubes increased TNF-α production and cell apoptosis [37].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [37]

    The Results report that HDAC2 siRNA increased TNF-α production and apoptosis in cultured primary skeletal muscle cells. The Methods describe these cells and their transfection but do not identify them as myotubes, so that more specific cell description is unsupported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • HDAC2 level is decreased in the quadriceps of COPD patients, associated with an increase in the NF-κB pathway.

    “The authors also evidenced a decrease of HDAC2 level in the quadriceps of COPD patients, associated with an increase in the NF-кB pathway.”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [37]

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Authors
To, M., Swallow, E. B., Akashi, K., Haruki, K., Natanek, S. A., Polkey, M. I., Ito, K., & Barnes, P. J.
Affiliations
  • Dokkyo University (JP)
  • NIHR Royal Brompton Respiratory Biomedical Research Unit (GB)
  • Imperial College London (GB)
Corresponding author
Barnes, Peter J.
ORCID
Venue
Respiratory Research
Publisher
Springer Science and Business Media LLC
Published
2017-05-19
Volume
18
Issue
1
Pages
99-99
ISSN
  • 1465-9921 (ISSN-L)
  • 1465-993X
DOI
10.1186/s12931-017-0588-8
PMC
PMC5438490
OpenAlex
W2616123180
Cited by
31
References
1
Citations by year
2026: 5 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 4
FWCI
1.12
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Respiratory Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
Wellcome Trust (076472/Z/05/Z)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Keywords
chronic obstructive pulmonary disease, skeletal muscle weakness, HDAC2, HDAC5, histone deacetylase, NF-κB, muscle protein expression, FEV1, maximal voluntary contraction, smoking, quadriceps, muscle biopsy, exercise capacity, muscle strength, lung function decline
MeSH terms
Aged, Female, Humans, Male, Middle Aged, NF-kappa B, Muscle, Skeletal, Muscle Weakness, Pulmonary Disease, Chronic Obstructive, Histone Deacetylase 2

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