COPD is accompanied by co-ordinated transcriptional perturbation in the quadriceps affecting the mitochondria and extracellular matrix.
Saffron A G Willis-OwenAnna ThompsonPaul R KempMichael I PolkeyWilliam O C M CooksonMiriam F MoffattSamantha A NatanekPublished in: Scientific reports (2018)
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.
Keyphrases
- extracellular matrix
- chronic obstructive pulmonary disease
- lung function
- network analysis
- oxidative stress
- skeletal muscle
- genome wide
- end stage renal disease
- transcription factor
- long non coding rna
- healthcare
- cell proliferation
- cystic fibrosis
- genome wide association
- chronic kidney disease
- palliative care
- ejection fraction
- signaling pathway
- cell death
- atrial fibrillation
- peritoneal dialysis
- heart failure
- prognostic factors
- single cell
- pain management
- quality improvement
- anterior cruciate ligament
- copy number
- heat shock
- chronic pain
- heat stress
- affordable care act