{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:59:51Z","timestamp":1790089191526,"version":"4.0.1"},"reference-count":53,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"Hurvis Foundation"},{"name":"Rhematology Research Foundation"},{"DOI":"10.13039\/501100013671","name":"Sun Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070764"],"award-info":[{"award-number":["32070764"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:p> Epithelial-mesenchymal transition (EMT) creates an environment facilitating fibrosis following alveolar epithelial cell injury. IL-23 has important roles in chronic autoimmune conditions like rheumatoid arthritis (RA), but its role in the interstitial lung disease that affects patients with RA is unclear. This study aimed to determine the profibrogenic role of IL-23 on somatic alveolar type I (ATI) epithelial cells. Primary ATI cells were isolated from rats and cultured on plastic dishes for 1\u20133 wk. After prolonged culture (\u226514 days) on rigid culture dishes, primary ATI cells gradually acquired a mesenchymal phenotype, identified by decreased expression of caveolin-1, and reorganization of F-actin cytoskeleton, indicating the initiation of EMT by matrix stiffness. To determine how IL-23 promotes EMT in vitro, transitioning ATI cells, cultured on a stiff substrate for \u226514 days were stimulated with IL-23. The EMT phenotype was significantly enhanced by IL-23, which upregulated \u03b1-smooth muscle actin (\u03b1-SMA), collagen I\/III protein, and decreased caveolin-1. Furthermore, IL-23 significantly promoted cell invasion, as well as apoptotic resistance on transitioning ATI cells. Mechanistically, IL-23-induced EMT was mammalian target of rapamycin\/ribosomal protein S6 (mTOR\/S6) signaling dependent and reversible by rapamycin. Transcriptional sequencing analysis of human lung fibrosis biopsy tissue revealed key roles for IL-23 in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This result was further validated by significantly upregulated IL-23 expression at the mRNA level in RA-ILD lung sections. Notably, transitioning ATI epithelial cells were abundantly detected in RA-ILD tissue. Taken together, these data support a role for IL-23 in the pathogenesis of RA lung fibrosis by promoting EMT in alveolar epithelial cells through mTOR\/S6 signaling. <\/jats:p>","DOI":"10.1152\/ajplung.00292.2021","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T14:21:44Z","timestamp":1632925304000},"page":"L1006-L1022","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["IL-23 amplifies the epithelial-mesenchymal transition of mechanically conditioned alveolar epithelial cells in rheumatoid arthritis-associated interstitial lung disease through mTOR\/S6 signaling"],"prefix":"10.1152","volume":"321","author":[{"given":"Chujie","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota"},{"name":"Department of Respiratory and Critical Care Medicine, West China 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