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Cited by 68Muscle Physiology and DisordersMicroRNA in disease regulationNutrition and Health in Aging

Increased Expression of H19/MiR-675 Is Associated with a Low Fat-Free Mass Index in Patients with COPD

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Lewis, Amy, Lee, Jen Y., Donaldson, Anna V., Natanek, S. Amanda, Vaidyanathan, Srividya, Man, William D.‐C., Hopkinson, Nicholas S., Sayer, Avan A. +5 more·2016·Journal of Cachexia, Sarcopenia and Muscle
DOI 10.1002/jcsm.12078PMC PMC4863928
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Abstract

Background: Loss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro . The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men. Methods: We identified miRNAs associated with a low fat‐free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR‐675 and miR‐519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community‐dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence. Results: Imprinted miRNAs (miR‐675 and from a cluster, C19MC which includes miR‐519a) were differentially expressed in the quadriceps of patients with a low fat‐free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR‐675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR‐519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Study. Relative methylation of the H19 ICR was reduced in COPD patients with muscle weakness but was not associated with FFM. In vitro , miR‐675 inhibited myoblast proliferation and patients with a low FFMI had fewer centralized nuclei suggesting miR‐675 represses regeneration. Conclusions: The data suggest that increased expression of miR‐675/H19 and altered methylation of the H19 imprinting control region are associated with a low FFMI in patients with COPD but not in healthy community dwelling older men suggesting that epigenetic control of this loci may contribute to a susceptibility to a low FFMI.

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Authors
Lewis, A., Lee, J. Y., Donaldson, A. V., Natanek, S. A., Vaidyanathan, S., Man, W. D. ‐., Hopkinson, N. S., Sayer, A. A., Patel, H. P., Cooper, C., Syddall, H., Polkey, M. I., & Kemp, P. R.
Affiliations
  • Imperial College London (GB)
  • Royal Brompton & Harefield NHS Foundation Trust (GB)
  • Southampton General Hospital (GB)
Corresponding author
Kemp, Paul R.
ORCID
Venue
Journal of Cachexia, Sarcopenia and Muscle
Publisher
Wiley
Published
2016-01-05
Volume
7
Issue
3
Pages
330-344
ISSN
  • 2190-5991 (ISSN-L)
  • 2190-6009
DOI
10.1002/jcsm.12078
PMC
PMC4863928
OpenAlex
W2215473048
Cited by
68
References
2
Citations by year
2026: 4 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 10 · 2018: 11 · 2017: 13 · 2016: 4
FWCI
6.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
  • Biotechnology and Biological Sciences Research Council
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
chronic obstructive pulmonary disease, miR-675, H19, C19MC, fat-free mass index, muscle mass, muscle strength, sarcopenia, muscle regeneration, DNA methylation, myoblast proliferation, quadriceps

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