{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:45:36Z","timestamp":1791989136722,"version":"4.4.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/501100008990","name":"Science and Technology Department of Zhejiang Province","doi-asserted-by":"publisher","award":["2019C03042"],"award-info":[{"award-number":["2019C03042"]}],"id":[{"id":"10.13039\/501100008990","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:p> Cachexia is a complex metabolic syndrome that occurs in approximately 50% of patients with cancer. Skeletal muscle atrophy is the primary clinical feature. Interleukin (IL)-17A, a proinflammatory factor, plays an important role in many chronic inflammatory diseases. Here, we describe a novel signaling pathway through which IL-17A induced muscle atrophy. We conducted a retrospective clinical study to investigate the relationship between IL-17A and the skeletal muscle index in patients with lung adenocarcinoma. We also investigated the involvement of JAK2\/STAT3 signaling pathway regarding the main features of cachexia by injecting Lewis lung carcinoma (LLC) cells into C57BL\/6 mice as a model to replicate cancer-induced cachexia. In vitro, C2C12 myotubes were treated with recombinant IL-17A, anti-IL-17A monoclonal antibody, STAT3 inhibitor AG490, and LLC-conditioned medium. Cell viability and aging were also evaluated. We found that in cancer conditions, increased serum levels of IL-17A were related to muscle wasting. JAK2\/STAT3 phosphorylation was observed in the muscle of LLC tumor-bearing mice, accompanied by decreased MHC\/Myog levels and increased MuRF1\/Atrogin-1 levels. Administration of anti-IL-17A monoclonal antibody and AG490 slowed muscle atrophy development. Consistent with the in vivo findings, C2C12 myotubes treated with IL-17A and LLC-conditioned medium demonstrated phosphorylated JAK2\/STAT3 signaling, resulting in MHC loss and myotube atrophy. IL-17A also inhibited C2C12 cell proliferation, cell cycle breaking, and cellular senescence. Our results identify that phosphorylation of IL-17A\/JAK2\/STAT3 signaling pathway appears to be an important component in the pathogenesis of LLC tumor-induced cachexia. Targeted therapy of IL-17A may be a promising approach to reduce skeletal muscle loss in patients with cancer. <\/jats:p>","DOI":"10.1152\/ajpcell.00463.2021","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T19:17:16Z","timestamp":1648063036000},"page":"C814-C824","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["IL-17A contributes to skeletal muscle atrophy in lung cancer-induced cachexia via JAK2\/STAT3 pathway"],"prefix":"10.1152","volume":"322","author":[{"given":"Lin","family":"Ying","sequence":"first","affiliation":[{"name":"Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, 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