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Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) contribute to muscle wasting. We hypothesised that ER stress is increased in muscles of bronchiectasis patients with sarcopenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the vastus lateralis (VL) of patients with bronchiectasis and sarcopenia (n=20) and healthy controls (n=10), markers indicative of ER stress, key components of the UPR signalling network, including activating transcription factor 6 (ATF6), protein kinase RNA-like ER kinase and inositol-requiring enzyme 1, and molecular indicators of proteolytic activity and autophagy were measured. Patients and controls were clinically evaluated. Patients were clinically stable, nonsmokers and had mild to moderate disease severity (bronchiectasis severity index score), and exhibited significantly reduced body weight, body mass index (BMI), fat-free mass index (FFMI), quadriceps maximal voluntary contraction (QMVC), handgrip strength and exercise capacity compared to the age- and sex-matched controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the VL of patients compared to the controls, ER stress markers activating transcription factor 4 (ATF4) and X-box binding protein (XBP1) levels and those of atrogin-1, muscle ring finger 1, 20S proteasome C8 subunit and nucleoporin p-62 increased, while inverse correlations were detected between muscle protein atrogin-1 levels and BMI, FFMI and nondominant QMVC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bronchiectasis patients with sarcopenia exhibit marked skeletal muscle impairment, systemic inflammation and selective activation of the ATF4 and XBP1 arms of the UPR. These molecular alterations were accompanied by increased proteolysis and signs of impaired autophagy. Targeting these pathways may offer novel therapeutic strategies to preserve muscle mass and function in bronchiectasis, ultimately improving quality of life and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/23120541.00746-2025","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T12:00:11Z","timestamp":1771588811000},"page":"00746-2025","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Selective activation of the unfolded protein response and proteolytic pathways in sarcopenic limb muscles of bronchiectasis patients"],"prefix":"10.1183","volume":"12","author":[{"given":"Adriana","family":"N\u00fa\u00f1ez-Robainas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Solano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Marsico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariela","family":"Alvarado-Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4359-0866","authenticated-orcid":false,"given":"Maria Cinta","family":"Cumpli-Gargallo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"S\u00e1inz-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Maiques","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2708-3443","authenticated-orcid":false,"given":"Esther","family":"Barreiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"81","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"2026050510154644000_12.2.00746-2025.1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.062026"},{"key":"2026050510154644000_12.2.00746-2025.2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00104909"},{"key":"2026050510154644000_12.2.00746-2025.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2008.06.013"},{"key":"2026050510154644000_12.2.00746-2025.4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1164\/rccm.201402-0373ST","article-title":"An official American Thoracic Society\/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease","volume":"189","author":"Maltais","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"2026050510154644000_12.2.00746-2025.5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201710-2140CI"},{"key":"2026050510154644000_12.2.00746-2025.6","doi-asserted-by":"crossref","first-page":"11315","DOI":"10.1002\/jcp.27789","article-title":"Endoplasmic reticulum stress and unfolded protein response profile in quadriceps of sarcopenic patients with respiratory diseases","volume":"234","author":"Barreiro","year":"2019","journal-title":"J Cell Physiol"},{"key":"2026050510154644000_12.2.00746-2025.7","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1152\/japplphysiol.00670.2018","article-title":"Endoplasmic reticulum stress and unfolded protein response in diaphragm muscle dysfunction of patients with stable chronic obstructive pulmonary disease","volume":"126","author":"Barreiro","year":"2019","journal-title":"J Appl Physiol (1985)"},{"key":"2026050510154644000_12.2.00746-2025.8","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.3390\/cancers11121929","article-title":"ER stress and unfolded protein response in cancer cachexia","volume":"11","author":"Roy","year":"2019","journal-title":"Cancers (Basel)"},{"key":"2026050510154644000_12.2.00746-2025.9","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14608"},{"key":"2026050510154644000_12.2.00746-2025.10","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201506-320KV"},{"key":"2026050510154644000_12.2.00746-2025.11","doi-asserted-by":"publisher","DOI":"10.3390\/life11040348"},{"key":"2026050510154644000_12.2.00746-2025.12","doi-asserted-by":"publisher","DOI":"10.1002\/bit.23282"},{"key":"2026050510154644000_12.2.00746-2025.13","first-page":"384","article-title":"The unfolded protein response: an overview","volume":"10","author":"Read","year":"2021","journal-title":"Biology (Basel)"},{"key":"2026050510154644000_12.2.00746-2025.14","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E13-11-0664"},{"key":"2026050510154644000_12.2.00746-2025.15","doi-asserted-by":"crossref","unstructured":"Gallot YS , Bohnert KR . 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