CoChat
Sign Up
Cited by 128Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchMicroRNA in disease regulation

Increased Skeletal Muscle-Specific MicroRNA in the Blood of Patients with COPD

Open access
Donaldson, Anna, Natanek, Samantha A, Lewis, Amy, Man, William D-C, Hopkinson, Nicholas S, Polkey, Michael I, Kemp, Paul R·2013·Thorax
DOI 10.1136/thoraxjnl-2012-203129PMC PMC3841809
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) carries a poor prognosis, therefore a non-invasive marker of this process could be useful. Reduced expression of muscle-specific microRNA (myomiRs) in quadriceps muscle in patients with COPD is associated with skeletal muscle weakness and changes in muscle fibre composition. Circulating exosomal miRNAs can be measured in blood, making them candidate biomarkers of biopsy phenotype. To determine whether plasma myomiR levels were associated with fibre size or fibre proportion, we measured myomiRs in plasma from patients with COPD and healthy controls. METHODS AND RESULTS: 103 patients with COPD and 25 age-matched controls were studied. Muscle-specific miRNA was elevated in the plasma of patients with COPD and showed distinct patterns. Specifically, miR-1 was inversely associated with fat-free mass in the cohort, whereas levels of miR-499 were more directly associated with strength and quadriceps type I fibre proportion. Two miRs not restricted to muscle in origin (miR-16 and miR-122) did not differ between patients and controls. Plasma miR-499 was also associated with muscle nuclear factor κB p50 but not p65 in patients with early COPD whereas plasma inflammatory cytokines were associated with miR-206 in patients with more advanced disease. CONCLUSIONS: Plasma levels of individual myomiRs are altered in patients with COPD but alone do not predict muscle fibre size or proportion. Our findings are consistent with an increase in muscle wasting and turnover associated with the development of skeletal muscle dysfunction and fibre-type shift in patients with stable COPD.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1136/thoraxjnl-2012-203129

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Levels of miR-499 were associated with nuclear NF-κB p50 in mild/moderate COPD, whereas in severe and very severe disease, miR-206 and miR-133 were associated with circulating cytokines, emphasizing the link with inflammation.

    “Furthermore, levels of miR-499 were associated with nuclear NF-κB p50 in mild/moderate COPD, whereas in severe and very severe disease, miR-206 and miR-133 were associated with circulating cytokines, emphasizing the link with inflammation.”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [156]

  • Later, miR-1, miR-206, and miR-133 were found significantly elevated in the plasma of patients with COPD, as well as miR-499, encoded within the slow myosin heavy chain gene and thus promoting type I fibers.

    “Later, miR-1, miR-206, and miR-133 were found significantly elevated in the plasma of patients with COPD, as well as miR-499, encoded within the slow myosin heavy chain (MHC) gene and thus promoting type I fibers [156].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [156]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 35

  1. [1]Bernard S LBP Whittom F Carrier G Peripheral muscle weakness in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 158: 629– 34 9700144
  2. [2]Gosker HR Engelen MP van Mameren H Muscle fiber type IIX atrophy is involved in the loss of fat-free mass in chronic obstructive pulmonary disease. Am J Clin Nutr 2002; 76: 113– 19 12081824
  3. [3]Natanek SA Gosker HR Slot IG Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (COPD); implications for stratified medicine? Muscle Nerve 2013; Published Online First 30 January 2013 10.1002/mus.23784 23553751 · DOI
  4. [4]Gosker HR van Mameren H van Dijk PJ Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease. Eur Respir J 2002; 19: 617– 25 11998989
  5. [5]Kelly JL Elkin SL Fluxman J Breathlessness and skeletal muscle weakness in patients undergoing lung health screening in primary care. COPD; 10: 40– 54 23272667
  6. [6]Seymour JM Spruit MA Hopkinson NS The prevalence of quadriceps weakness in COPD and the relationship with disease severity. Eur Respir J 2010; 36: 81– 8 19897554 PMC3039205
  7. [8]Swallow EB Reyes D Hopkinson NS Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease. Thorax 2007; 62: 115– 20 17090575 PMC2111256
  8. [9]Jakobsson P Jorfeldt L Brundin A Skeletal muscle metabolites and fibre types in patients with advanced chronic obstructive pulmonary disease (COPD), with and without chronic respiratory failure. Eur Respir J 1990; 3: 192– 6 2311744
  9. [10]Whittom F Jobin J Simard PM Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. Med Sci Sports Exerc 1998; 30: 1467– 74 9789845
  10. [11]Maltais F Sullivan MJ LeBlanc P Altered expression of myosin heavy chain in the vastus lateralis muscle in patients with COPD. Eur Respir J 1999; 13: 850– 4 10362052
  11. [12]Satta A Migliori GB Spanevello A Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance. Eur Respir J 1997; 10: 2853– 60 9493673
  12. [13]Gosker H Zeegers M Wouters E Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis. Thorax 2007; 62: 944– 9 17526675 PMC2117111
  13. [14]Steiner MC Roubenoff R Tal-Singer RM Prospects for the development of effective pharmacotherapy targeted at the skeletal muscles in chronic obstructive pulmonary disease. A translational review. Thorax 2012; 67: 1102– 9 22561528
  14. [15]Chen JF Mandel EM Thomson JM The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 2006; 38: 228– 33 16380711 PMC2538576
  15. [16]Guller I Russell AP MicroRNAs in skeletal muscle: their role and regulation in development, disease and function. J Physiol 2010; 588(Pt 21): 4075– 87 20724363 PMC3002442
  16. [17]van Rooij E Quiat D Johnson BA A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell 2009; 17: 662– 73 19922871 PMC2796371
  17. [18]McCarthy JJ Esser KA Peterson CA Evidence of MyomiR network regulation of beta-myosin heavy chain gene expression during skeletal muscle atrophy. Physiol Genomics 2009; 39: 219– 26 19690046 PMC2789671
  18. [19]Lewis A Riddoch-Contreras J Natanek SA Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax 2012; 67: 26– 34 21998125 PMC3240776
  19. [20]Mitchell PS Parkin RK Kroh EM Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008; 105: 10513– 18 18663219 PMC2492472
  20. [21]Alevizos I Illei GG MicroRNAs as biomarkers in rheumatic diseases. Nat Rev Rheumatol 2010; 6: 391– 8 20517293 PMC3041596
  21. [22]Rabe KF Hurd S Anzueto A Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007; 176: 532– 55 17507545
  22. [23]Natanek SA Riddoch-Contreras J Marsh GS Yin Yang 1 expression and localisation in quadriceps muscle in COPD. Arch Bronconeumol 2011; 47: 296– 302 21565439
  23. [24]Riddoch-Contreras J George T Natanek SA p38 Mitogen-activated protein kinase is not activated in the quadriceps of patients with stable chronic obstructive pulmonary disease. COPD 2012; 9: 142– 50 22409248
  24. [26]Ellis PD Smith CW Kemp P Regulated tissue-specific alternative splicing of enhanced green fluorescent protein transgenes conferred by alpha-tropomyosin regulatory elements in transgenic mice. J Biol Chem 2004; 279: 36660– 9 15194683
  25. [27]Kroh EM Parkin RK Mitchell PS Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 2010; 50: 298– 301 20146939 PMC4186708
  26. [28]Chang J Nicolas E Marks D miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 2004; 1: 106– 13 17179747
  27. [29]Cacchiarelli D Legnini I Martone J miRNAs as serum biomarkers for Duchenne muscular dystrophy. EMBO Mol Med 2011; 3: 258– 65 21425469 PMC3112257
  28. [30]Hu Z Chen X Zhao Y Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol 2010; 28: 1721– 6 20194856
  29. [31]Hunter RB Kandarian SC Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy. J Clin Invest 2004; 114: 1504– 11 15546001 PMC525738
  30. [32]Collino F Deregibus MC Bruno S Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One 2010; 5: e11803 20668554 PMC2910725
  31. [33]Kim HK Lee YS Sivaprasad U Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol 2006; 174: 677– 87 16923828 PMC2064311
  32. [34]Dey BK Gagan J Dutta A miR-206 and -486 induce myoblast differentiation by downregulating Pax7. Mol Cell Biol 2011; 31: 203– 14 21041476 PMC3019853
  33. [35]Fichtlscherer S Zeiher AM Dimmeler S Circulating microRNAs: biomarkers or mediators of cardiovascular diseases? Arterioscler Thromb Vasc Biol 2011; 31: 2383– 90 22011751
  34. [36]Seymour JM Ward K Raffique A Quadriceps and ankle dorsiflexor strength in chronic obstructive pulmonary disease. Muscle Nerve 2012; 46: 548– 54 22987696
  35. [37]Stubbings AK Moore AJ Dusmet M Physiological properties of human diaphragm muscle fibres and the effect of chronic obstructive pulmonary disease. J Physiol 2008; 586: 2637– 50 18372305 PMC2464347

Cited by

Sorted by citations

Authors
Donaldson, A., Natanek, S. A., Lewis, A., Man, W. D.-C., Hopkinson, N. S., Polkey, M. I., & Kemp, P. R.
Affiliations
  • Royal Brompton Hospital (GB)
  • Imperial College London (GB)
Corresponding author
Kemp, Paul R
ORCID
Venue
Thorax
Publisher
BMJ
Published
2013-06-28
Volume
68
Issue
12
Pages
1140-1149
ISSN
  • 0040-6376 (ISSN-L)
  • 1468-3296
DOI
10.1136/thoraxjnl-2012-203129
PMC
PMC3841809
OpenAlex
W2121692358
Cited by
128
References
1
Citations by year
2026: 3 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 5 · 2018: 10 · 2017: 18 · 2016: 19 · 2015: 13 · 2014: 17 · 2013: 2
FWCI
7.62
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)
Funders
  • Royal Brompton and Harefield NHS Foundation Trust
  • National Institute for Health and Care Research (DHCS/07/07/009, CTF-01-12-04)
  • Imperial College London
  • Medical Research Council (G1001362)
  • Biotechnology and Biological Sciences Research Council (BB/H530703/1)
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, skeletal muscle weakness, muscle-specific microRNAs, miR-499, miR-1, miR-206, muscle fiber composition, fat-free mass, muscle strength, muscle atrophy, NF-κB p50, inflammatory cytokines, biomarkers
MeSH terms
Aged, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Biomarkers, Case-Control Studies, Cytokines, Muscle Fibers, Slow-Twitch, Muscle Weakness, Pulmonary Disease, Chronic Obstructive, MicroRNAs, Transcription Factor RelA, NF-kappa B p50 Subunit, Quadriceps Muscle, Muscle Strength

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review