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Differentially co-expressed myofibre transcripts associated with abnormal myofibre proportion in chronic obstructive
Joe W Chiles1, Ava C Wilson1,2, Rachel Tindal3
1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Journal of Cachexia, Sarcopenia and Muscle
|April 22, 2024
Summary
Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) involves abnormal muscle fiber proportions. This study identified specific gene expression patterns linked to this phenotype, offering insights into COPD
Area of Science:
- Pulmonary Medicine
- Skeletal Muscle Physiology
- Molecular Biology
Background:
- Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD).
- Previous studies linked altered myosin heavy chain expression to COPD severity, primarily in male cohorts.
- This study aimed to define abnormal myofibre proportion in both sexes and identify associated transcriptional changes in COPD.
Purpose of the Study:
- To define an abnormal myofibre proportion phenotype in males and females with COPD.
- To identify specific transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD patients.
- To investigate the relationship between myofibre proportion, clinical characteristics, and gene expression in COPD.
Main Methods:
- Assessed 46 COPD participants for body composition, strength, endurance, and pulmonary function.
- Analyzed vastus lateralis muscle biopsies for fibre-type distribution and gene expression via immunofluorescence and RNA-sequencing.
- Utilized sex-stratified k-means clustering to define abnormal myofibre proportion and correlated transcripts/networks with this phenotype.
Main Results:
- Defined abnormal myofibre proportion criteria for males and females with COPD; half of participants met these criteria.
- Participants with abnormal myofibre proportion exhibited lower handgrip strength, 6-min walk distance, and FEV1/FVC ratio.
- Identified 29 transcripts associated with abnormal myofibre proportion, including NEB, TPM1, and TPM2; two co-expression modules linked to muscle atrophy and bone mineral density loci were identified.
Conclusions:
- Significant transcriptional alterations are associated with abnormal myofibre proportions in COPD patients.
- A co-expression network linked to abnormal myofibre proportion was enriched for transcripts of both type I and type IIa fibres.
- Findings suggest altered transcriptional regulation across multiple muscle fibre types in COPD-related skeletal muscle dysfunction.
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