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Cited by 156Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchMicroRNA in disease regulation

Downregulation of the Serum Response Factor/MiR-1 Axis in the Quadriceps of Patients with COPD

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Lewis, Amy, Riddoch-Contreras, Joanna, Natanek, Samantha A, Donaldson, Anna, Man, William D-C, Moxham, John, Hopkinson, Nicholas S, Polkey, Michael I +1 more·2012·Thorax
DOI 10.1136/thoraxjnl-2011-200309PMC PMC3240776
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Abstract

RATIONALE: Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised. Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression. The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown. METHODS: 31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy. The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR. RESULTS: A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B mRNA: fourfold, p=0.011). miR-1 expression was associated with smoking history, lung function, fat-free mass index, 6 min walk distance and percentage of type 1 fibres. miR-133 and miR-206 were negatively correlated with daily physical activity. Insulin-like growth factor 1 mRNA was increased in the patients and miR-1 was negatively correlated with phosphorylation of the kinase Akt. Furthermore, the protein levels of histone deacetylase 4, another miR-1 target, were increased in the patients. CONCLUSIONS: Downregulation of the activity of the MRTF-SRF axis and the expression of muscle-specific microRNAs, particularly miR-1, may contribute to COPD-associated skeletal muscle dysfunction.

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  • miR-1 is associated with insulin-like growth factor-1 (IGF-1) regulation, providing a possible explanation for reduced protein synthesis.

    “miR-1 is also associated with insulin-like growth factor-1 (IGF-1) regulation, providing a possible explanation for reduced protein synthesis (cf. infra).”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [155]

    The Results (Reduced expression of targets of miR-1 in patients with COPD; page unavailable) report increased IGF-1 mRNA and an inverse association between miR-1 and Akt phosphorylation, supporting a link to IGF-1 regulation. The Discussion (miR-1 in muscle biology; page unavailable) raises synthetic resistance as a possible explanation for increased hypertrophy signalling despite muscle wasting, but does not establish that miR-1 regulation explains reduced protein synthesis. (LLM, conf=0.84)

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  • In the Lewis study, levels of miR-133 and miR-206 were unchanged.

    “In that study, levels of miR-133 and miR-206 were unchanged.”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [155]

  • HDAC4 is thought to inhibit regulators of myosin heavy chain 1 expression, thus possibly accounting for the switch in fiber type.

    “The latter is thought to inhibit regulators of myosin heavy chain 1 expression, thus possibly accounting for the switch in fiber type.”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [155]

  • Lewis and colleagues showed decreased expression of miR-1 in COPD quadriceps, as well as an increase in its target histone deacetylase 4 (HDAC4) at the protein level.

    “The pioneer study in the matter was conducted by Lewis and colleagues and showed a decreased expression of miR-1 in COPD quadriceps, as well as an increase in its target, histone deacetylase 4 (HDCA4) at the protein level [155].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [155]

  • Some studies report a counterintuitive rise of IGF-1 or Akt levels in COPD muscle, possibly due to a compensatory mechanism.

    “Meanwhile, some studies report a counterintuitive rise of IGF-1 or Akt levels [155,165], possibly due to a compensatory mechanism.”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [155]

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Authors
Lewis, A., Riddoch-Contreras, J., Natanek, S. A., Donaldson, A., Man, W. D.-C., Moxham, J., Hopkinson, N. S., Polkey, M. I., & Kemp, P. R.
Affiliations
  • Imperial College London (GB)
  • Royal Brompton & Harefield NHS Foundation Trust (GB)
  • King's College London (GB)
Corresponding author
Kemp, Paul R
ORCID
Venue
Thorax
Publisher
BMJ
Published
2011-10-13
Volume
67
Issue
1
Pages
26-34
ISSN
  • 0040-6376 (ISSN-L)
  • 1468-3296
DOI
10.1136/thoraxjnl-2011-200309
PMC
PMC3240776
OpenAlex
W2157135058
Cited by
156
References
2
Citations by year
2026: 5 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 13 · 2017: 16 · 2016: 20 · 2015: 18 · 2014: 20 · 2013: 17 · 2012: 9
FWCI
6.24
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Thorax (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by-nc)
Funders
  • Wellcome Trust
  • National Institute for Health and Care Research (DHCS/07/07/009)
  • Imperial College London
  • Biotechnology and Biological Sciences Research Council
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 › Cancer Research › MicroRNA in disease regulation
Keywords
chronic obstructive pulmonary disease, muscle atrophy, quadriceps, serum response factor, miR-1, MRTF, muscle-specific microRNAs, skeletal muscle dysfunction, insulin-like growth factor I, Akt phosphorylation, HDAC4, myosin heavy chain, physical activity, smoking
MeSH terms
Aged, Biopsy, Female, Fluorescent Antibody Technique, Follow-Up Studies, Humans, Male, Muscular Diseases, Signal Transduction, Down-Regulation, Disease Progression, Genetic Predisposition to Disease, Reverse Transcriptase Polymerase Chain Reaction, Serum Response Factor, Pulmonary Disease, Chronic Obstructive, MicroRNAs, Quadriceps Muscle

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