Kritikaki Efpraxia, Terzis Gerasimos, Soundararajan Meera, Vogiatzis Ioannis, Simoes Davina C M
Faculty of Health and Life Sciences, Northumbria University Newcastle, Newcastle upon Tyne, UK.
School of Physical Education and Sports Science, National and Kapodistrian University of Athens, Athens, Greece.
ERJ Open Res. 2024 May 27;10(3). doi: 10.1183/23120541.00857-2023. eCollection 2024 May.
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).
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).
Atrophic COPD patients presented a lower average vastus lateralis muscle fibre cross-sectional area (3872±258 μm) compared to non-atrophic COPD (4509±198 μm). Gene expression of ECM molecules was found significantly lower in atrophic COPD compared to non-atrophic COPD for collagen type I alpha 1 chain (), fibronectin (), tenascin C () and biglycan () In terms of protein levels, there were no significant differences between the two COPD cohorts for any of the ECM molecules tested.
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.
细胞外基质（ECM）蛋白是肌肉细胞微环境的主要成分，具有指导性信号传导、引导细胞行为和控制肌肉再生的作用。ECM重塑是慢性阻塞性肺疾病（COPD）和衰老肌肉中受影响最严重的信号通路之一。由于部分COPD患者存在肌肉萎缩，我们质疑与无肌肉萎缩（非萎缩性COPD）的患者相比，外周肌肉萎缩（萎缩性COPD）患者的ECM组成是否会发生改变。
使用酶联免疫吸附测定（ELISA）和实时聚合酶链反应（PCR）对29例COPD患者（1秒用力呼气量为预测值的55±12%）股外侧肌活检样本中一组已知对肌生成有影响的ECM分子进行定量分析。根据去脂体重指数（<17或≥17 kg·m）将COPD患者分为萎缩性或非萎缩性组。
与非萎缩性COPD患者（4509±198μm）相比，萎缩性COPD患者的股外侧肌平均纤维横截面积较低（3872±258μm）。与非萎缩性COPD相比，萎缩性COPD患者中I型胶原蛋白α1链、纤连蛋白、腱生蛋白C和双糖链蛋白聚糖的ECM分子基因表达显著降低。在蛋白质水平上，两个COPD队列中所检测的任何ECM分子之间均无显著差异。
尽管萎缩性COPD患者的收缩性肌肉组织减少，但萎缩性和非萎缩性COPD患者之间ECM mRNA表达的差异在蛋白质水平上并未体现，这可能表明存在长寿ECM蛋白的积累和蛋白稳态失调，这在失健和衰老过程中通常会观察到。
