Expression of intramuscular extracellular matrix proteins in vastus lateralis muscle fibres between atrophic and non-atrophic COPD

BACKGROUND: Extracellular matrix (ECM) proteins are the major constituents of the muscle cell micro-environment, imparting instructive signalling, steering cell behaviour and controlling muscle regeneration. ECM remodelling is among the most affected signalling pathways in COPD and aged muscle. As a fraction of COPD patients present muscle atrophy, we questioned whether ECM composition would be altered in patients with peripheral muscle wasting (atrophic COPD) compared to those without muscle wasting (non-atrophic COPD).

METHODS: A set of ECM molecules with known impact on myogenesis were quantified in vastus lateralis muscle biopsies from 29 COPD patients (forced expiratory volume in 1 s 55±12% predicted) using ELISA and real-time PCR. COPD patients were grouped to atrophic or non-atrophic based on fat-free mass index (<17 or ≥17 kg·m -2).

RESULTS: Atrophic COPD patients presented a lower average vastus lateralis muscle fibre cross-sectional area (3872±258 μm 2) compared to non-atrophic COPD (4509±198 μm 2). Gene expression of ECM molecules was found significantly lower in atrophic COPD compared to non-atrophic COPD for collagen type I alpha 1 chain ( COL1A1), fibronectin ( FN1), tenascin C ( TNC) and biglycan ( BGN) . In terms of protein levels, there were no significant differences between the two COPD cohorts for any of the ECM molecules tested.

CONCLUSIONS: Although atrophic COPD presented decreased contractile muscle tissue, the differences in ECM mRNA expression between atrophic and non-atrophic COPD were not translated at the protein level, potentially indicating an accumulation of long-lived ECM proteins and dysregulated proteostasis, as is typically observed during deconditioning and ageing.