Differences in micro-RNA expression profile between vastus lateralis samples and myotubes in COPD cachexia

Abstract

Quadriceps muscle weakness and wasting are common comorbidities in chronic obstructive pulmonary disease (COPD). Micro-RNA expression upregulation may favor muscle mass growth and differentiation. We hypothesized that the profile of muscle-enriched micro-RNAs in cultured myotubes differs between patients with COPD of a wide range of body composition and healthy controls and that expression levels of those micro-RNAs from patients with COPD and controls differ between in vivo and in vitro conditions. Twenty-nine patients with COPD [ n = 15 with muscle wasting and fat-free mass index (FFMI) 15 kg/m2 and n = 14 with normal body composition and FFMI 18 kg/m2] and 10 healthy controls (FFMI 19 kg/m2) were consecutively recruited. Biopsies from the vastus lateralis muscle were obtained in all study subjects. A fragment of each biopsy was used to obtain primary cultures, in which muscle cells were first proliferated to be then differentiated into actual myotubes. In both sets of experiments (in vivo biopsies and in vitro myotubes) the following muscle-enriched micro-RNAs from all the study subjects were analyzed using quantitative real-time PCR amplification: micro-RNA (miR)-1, miR-133a, miR-206, miR-486, miR-29b, miR-27a, and miR-181a. Whereas the expression of miR-1, miR-206, miR-486, and miR-29b was upregulated in the muscle biopsies of patients with COPD compared with those of healthy controls, levels of none of the studied micro-RNAs in the myotubes (primary cultured cells) significantly differed between patients with COPD and the controls. We conclude from these findings that environmental factors (blood flow, muscle metabolism, and inflammation) taking place in vivo (biopsies) in muscles may account for the differences observed in micro-RNA expression between patients with COPD and controls. In the myotubes, however, the expression of the same micro-RNAs did not differ between the study subjects as such environmental factors were not present. These findings suggest that therapeutic strategies should rather target environmental factors in COPD muscle wasting as the profile of micro-RNA expression in myotubes was similar in patients to that observed in the healthy controls. NEW & NOTEWORTHY Environmental factors taking place in vivo (biopsies) in the muscles may explain differences observed in micro-RNA expression between patients with chronic obstructive pulmonary disease (COPD) and controls. In the myotubes, however, the expression of the same micro-RNAs did not differ between the study subjects as such environmental factors were not present. These findings suggest that therapeutic strategies should rather target environmental factors in COPD muscle wasting and cachexia as micro-RNA expression profile in myotubes was similar between patients and controls.

Expression Analysis of Muscle-Specific miRNAs in Plasma-Derived Extracellular Vesicles from Patients with Chronic Obstructive Pulmonary Disease

“…Regarding miR-206, our data are in line with previous evidence from other laboratories showing the upregulation of miR-206 in lung tissues [27], limb muscles [28] and vastus lateralis muscle [29] of patients with COPD compared to healthy subjects, its increased level in the plasma of COPD patients [30] and its inverse association with daily physical activity in the same patients [31]. Further suggestive reports from the literature reveal miR-206 to be upregulated during skeletal muscle regeneration and able to promote differentiation of skeletal muscle satellite cells in vitro [32][33][34].…”

Update on the Etiology, Assessment, and Management of COPD Cachexia: Considerations for the Clinician

“… 42 Additionally, cachectic patients with COPD have dysregulated micro-RNA expression related to muscle proliferation and differentiation during myogenesis compared to patients without cachexia. 43 …”

“…42 Additionally, cachectic patients with COPD have dysregulated micro-RNA expression related to muscle proliferation and differentiation during myogenesis compared to patients without cachexia. 43 The molecular and cellular mechanisms responsible for fat mass loss, mostly observed in patients with advanced COPD and particularly emphysematous COPD, 26 have received less attention. Most scientific work has focused on the role of adipokines, cell-signaling molecules (cytokines), produced by the adipose tissue.…”

Effects of eccentric, concentric and eccentric/concentric training on muscle function and mass, functional performance, cardiometabolic health, quality of life and molecular adaptations of skeletal muscle in COPD patients: a multicentre randomised trial

“…Farre-Garros et al showed that muscle miR-542-3p and miR-542-5p were associated with muscle dysfunction and could suppress muscle protein synthesis in COPD [ 49 ]. Furthermore, Barreiro et al showed that the levels of muscle miR-1, miR-206, miR-486, miR-29b, miR-133a, miR-27a, and miR-181a were lower in COPD patients with muscle wasting [ 50 ]. Interestingly, miR-208b and miR-499 have shown to be encoded in type I fibres only [ 51 ].…”