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Cited by 42Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchMitochondrial Function and Pathology

COPD Is Accompanied by Co-Ordinated Transcriptional Perturbation in the Quadriceps Affecting the Mitochondria and Extracellular Matrix

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Willis-Owen, Saffron A. G., Thompson, Anna, Kemp, Paul R., Polkey, Michael I., Cookson, William O. C. M., Moffatt, Miriam F., Natanek, Samantha A.·2018·Scientific Reports
DOI 10.1038/s41598-018-29789-6PMC PMC6093887
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Abstract

Skeletal muscle dysfunction is a frequent extra-pulmonary manifestation of Chronic Obstructive Pulmonary Disease (COPD) with implications for both quality of life and survival. The underlying biology nevertheless remains poorly understood. We measured global gene transcription in the quadriceps using Affymetrix HuGene1.1ST arrays in an unselected cohort of 79 stable COPD patients in secondary care and 16 healthy age- and gender-matched controls. We detected 1,826 transcripts showing COPD-related variation. Eighteen exhibited ≥2fold changes ( SLC22A3 , FAM184B , CDKN1A , FST , LINC01405 , MUSK , PANX1 , ANKRD1 , C12orf75 , MYH1 , POSTN , FRZB , TNC , ACTC1 , LINC00310 , MYH3 , MYBPH and AREG ). Thirty-one transcripts possessed previous reported evidence of involvement in COPD through genome-wide association, including FAM13A . Network analysis revealed a substructure comprising 6 modules of co-expressed genes. We identified modules with mitochondrial and extracellular matrix features, of which IDH2 , a central component of the mitochondrial antioxidant pathway, and ABI3BP , a proposed switch between proliferation and differentiation, represent hubs respectively. COPD is accompanied by coordinated patterns of transcription in the quadriceps involving the mitochondria and extracellular matrix and including genes previously implicated in primary disease processes.

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  • One transcriptomic study reported an increase in SLC22A3, a metabolic stress gene involved in AA transportation and histamine clearance, in COPD quadriceps.

    “Indeed, one study reported an increase in the COPD quadriceps of SLC22A3, a metabolic stress gene involved in AA transportation and histamine clearance [94].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [94]

    The Results report 3.35-fold greater SLC22A3 expression in COPD quadriceps than in healthy controls. The Discussion links the gene to a metabolic-stress theme and describes its role in organic-cation clearance, including a preference for histamine, but does not say it transports AA. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The transcriptome revealed an important lower expression of IDH2 in COPD quadriceps.

    “the transcriptome revealed an important lower expression of IDH2.”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [94]

  • In a cohort of 79 COPD patients, COPD was accompanied by coordinated patterns of transcription of genes involved in mitochondria function in the quadriceps.

    “In a cohort of 79 COPD patients, Willis-Owen and colleagues recently performed a nonbiased transcriptomic analysis and showed that COPD was accompanied by coordinated patterns of transcription of genes involved in mitochondria function in the quadriceps [94].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [94]

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References 51 · Cited by 42

Research works printed but not linked: 47

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Authors
Willis-Owen, S. A. G., Thompson, A., Kemp, P. R., Polkey, M. I., Cookson, W. O. C. M., Moffatt, M. F., & Natanek, S. A.
Affiliations
Imperial College London (GB)
Corresponding author
Natanek, Samantha A.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-08-15
Volume
8
Issue
1
Pages
12165-12165
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-29789-6
PMC
PMC6093887
OpenAlex
W2886498706
Cited by
42
References
51
Citations by year
2026: 2 · 2025: 6 · 2024: 7 · 2023: 4 · 2022: 11 · 2021: 4 · 2020: 4 · 2019: 4
FWCI
1.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • 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 (WT09694, WT 079686/Z/06/Z, 079686/Z/06/Z, WT097117, 079686, 096964/Z/11/Z)
  • Royal Brompton and Harefield NHS Foundation Trust
  • National Institute for Health and Care Research
  • Imperial College London
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 › Mitochondrial Function and Pathology
Keywords
chronic obstructive pulmonary disease, skeletal muscle dysfunction, quadriceps, gene expression profiling, mitochondrial function, extracellular matrix, IDH2, gene co-expression modules, FAM13A, extrapulmonary manifestations
MeSH terms
Aged, Extracellular Matrix, Female, Humans, Lung, Male, Middle Aged, Mitochondria, Quality of Life, Cohort Studies, Muscle, Skeletal, Gene Expression Profiling, Pulmonary Disease, Chronic Obstructive, Quadriceps Muscle, Genome-Wide Association Study, Transcriptome

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