{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:43:45Z","timestamp":1782312225826,"version":"3.54.5"},"reference-count":35,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:p>Loss of diaphragm muscle strength in inflammatory lung disease contributes to mortality and is associated with diaphragm fiber atrophy. Ubiquitin (Ub) 26S-proteasome system (UPS)-dependent protein breakdown, which mediates muscle atrophy in a number of physiological and pathological conditions, is elevated in diaphragm muscle of patients with chronic obstructive pulmonary disease. Nuclear factor kappa B (NF-\u03baB), an essential regulator of many inflammatory processes, has been implicated in the regulation of poly-Ub conjugation of muscle proteins targeted for proteolysis by the UPS. Here, we test if NF-\u03baB activation in diaphragm muscle and subsequent protein degradation by the UPS are required for pulmonary inflammation-induced diaphragm atrophy. Acute pulmonary inflammation was induced in mice by intratracheal lipopolysaccharide instillation. Fiber cross-sectional area, ex vivo tyrosine release, protein poly-Ub conjugation, and inflammatory signaling were determined in diaphragm muscle. The contribution of NF-\u03baB or the UPS to diaphragm atrophy was assessed in mice with intact or genetically repressed NF-\u03baB signaling or attenuated poly-Ub conjugation, respectively. Acute pulmonary inflammation resulted in diaphragm atrophy measured by reduced muscle fiber cross-sectional area. This was accompanied by diaphragm NF-\u03baB activation, and proteolysis, measured by tyrosine release from the diaphragm. Poly-Ub conjugation was increased in diaphragm, as was the expression of muscle-specific E3 Ub ligases. Genetic suppression of poly-Ub conjugation prevented inflammation-induced diaphragm muscle atrophy, as did muscle-specific inhibition of NF-\u03baB signaling. In conclusion, the present study is the first to demonstrate that diaphragm muscle atrophy, resulting from acute pulmonary inflammation, requires NF-\u03baB activation and UPS-mediated protein degradation.<\/jats:p>","DOI":"10.1152\/ajplung.00084.2011","type":"journal-article","created":{"date-parts":[[2011,10,15]],"date-time":"2011-10-15T02:43:03Z","timestamp":1318646583000},"page":"L103-L110","source":"Crossref","is-referenced-by-count":38,"title":["NF-\u03baB activation and polyubiquitin conjugation are required for pulmonary inflammation-induced diaphragm atrophy"],"prefix":"10.1152","volume":"302","author":[{"given":"Astrid","family":"Haegens","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemie M.","family":"Schols","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H.","family":"Gorissen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anon L.","family":"van Essen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Snepvangers","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Gray","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Canada; 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