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Proteolysis and Autophagy in the Vastus Lateralis of Patients With Bronchiectasis-associated Sarcopenia: Role in Training Programs

Year: 2026

Type: article

Abstract: Muscle dysfunction or sarcopenia is a systemic manifestation of chronic respiratory diseases such as COPD and non-cystic fibrosis (non-CF) bronchiectasis. Alterations in the endoplasmic reticulum (ER) as a signaling mechanism, as well as markers of proteolysis and autophagy, are increased in the vastus lateralis (VL) of COPD patients. Until now, it has not been demonstrated that these events occur in patients with bronchiectasis. The hypothesis is that expression of ER stress, proteolysis, and autophagy markers may be increased in the VL of patients with non-CF bronchiectasis-associated sarcopenia. To evaluate biomarkers of ER stress, proteolysis, and autophagy and explore correlations between biological findings and clinical muscle assessment parameters. In 20 stable patients with non-CF bronchiectasis and functionally confirmed sarcopenia, and 10 healthy subjects, levels of ER stress biomarkers (chaperone molecules and the IRE1, PERK, and ATF6 pathways), proteolysis markers (ubiquitin-proteasome system), and autophagy markers were quantified. Associations between clinical and biological variables were also assessed (Pearson correlation coefficient). Compared to controls, the VL of patients showed higher expression of ER stress markers (XBP1, ATF4), proteolysis markers (MURF1 and 20S proteasome), and autophagy marker (p62). In patients, BiP and calreticulin levels correlated negatively with fat-free mass index (FFMI) (r = -0.449, p = 0.047) and quadriceps strength (r = -0.443, p = 0.045), respectively. Protein degradation pathways, autophagy, and ER-mediated signalling are relevant in the pathophysiology of sarcopenia in patients with stable bronchiectasis. These findings may help explain the reduced response to exercise training in chronic respiratory patients.

Source: Open Respiratory Archives

DOI: 10.1016/j.opresp.2026.100546

Authors: Cinta Cumplí Gargallo, Adriana Núñez-Robainas, Mariela Alvarado-Miranda, Marina Sáinz, Esther Barreiro