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Irisin is being increasingly recognized for its therapeutic potential in attenuating pulmonary injury, but its underlying mechanism remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human lung tissue samples were subjected to IHC analysis for irisin, integrin \u03b1V\u03b25, and GRP78 expression. CSE+LPS-induced mouse and cell models were used to investigate whether irisin protects against emphysema and inflammation by regulating ER homeostasis and AMPK activity via integrin \u03b1V\u03b25.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In COPD patients, irisin levels are decreased, whereas integrin \u03b1V\u03b25 and GRP78 levels are elevated. Irisin improved lung function and attenuated emphysema and inflammation in mice, and these effects were abolished by cilengitide. Irisin directly bound to integrin \u03b1V\u03b25, maintained ER homeostasis via the PERK\/ATF4\/CHOP pathway, and activated AMPK. These protective effects were lost upon integrin \u03b1V\u03b25 knockdown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that through integrin \u03b1V\u03b25, irisin concurrently maintains ER homeostasis and activates AMPK, thereby alleviating CSE+LPS-induced emphysema and inflammation, suggesting a novel therapeutic direction for the management of AECOPD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-026-03850-9","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:56:46Z","timestamp":1785369406000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Irisin maintains ER homeostasis and activates AMPK via integrin \u03b1V\u03b25 to attenuate CSE\u2009+\u2009LPS-induced emphysema and inflammation"],"prefix":"10.1186","volume":"27","author":[{"given":"Zina","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongxinwei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiqing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"issue":"5","key":"3850_CR1","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/S2213-2600(21)00555-5","volume":"10","author":"A Agusti","year":"2022","unstructured":"Agusti A, Melen E, DeMeo DL, Breyer-Kohansal R, Faner R. 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