{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:44:02Z","timestamp":1777632242322,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Excessive inflammation and alveolar barrier dysfunction are commonly observed in acute respiratory distress syndrome (ARDS). ADAMTS2 is an ECM\u2010remodeling metalloproteinase with emerging immunomodulatory roles and may influence inflammatory injury and epithelial barrier stability via PI3K\/AKT\/mTOR signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptome sequencing of peripheral blood samples from ARDS patients revealed elevated ADAMTS2 expression. An in vitro ARDS model was established by stimulating human type II alveolar epithelial cells with LPS. The impact of ADAMTS2 silencing on inflammatory response, autophagic activity, tight junction proteins, and PI3K\/AKT\/mTOR signaling was examined through qRT\u2010PCR, Western blot, immunofluorescence, ELISA, and flow cytometry analyses. A rescue experiment was performed using the PI3K activator 740 Y\u2010P.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ADAMTS2 was significantly upregulated in ARDS transcriptomic analysis, with functional enrichment highlighting ECM\u2010related processes and PI3K\/AKT\/mTOR signaling. In LPS\u2010stimulated alveolar epithelial cells, ADAMTS2 expression was ~2.5\u20133.0\u2010fold higher than that in control cells. ADAMTS2 silencing reduced TNF\u2010\u03b1 and IL\u20101\u03b2 release by ~55%\u201360% and decreased apoptosis by ~30%, while improving barrier integrity (increased ZO\u20101\/Occludin levels and TEER). Autophagy\u2010related changes were observed upon ADAMTS2 knockdown, including increased Beclin\u20101 and LC3B\u2010II levels with reduced p62\/SQSTM1 accumulation. Mechanistically, ADAMTS2 knockdown attenuated PI3K\/AKT\/mTOR phosphorylation, and these protective effects were partially reversed by the PI3K agonist 740 Y\u2010P.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ADAMTS2 knockdown mitigated LPS\u2010induced epithelial injury and barrier dysfunction, in association with PI3K\/AKT\/mTOR signaling and autophagy\u2010related changes, suggesting ADAMTS2 as a potential therapeutic target for ARDS pending further in vivo validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70429","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:51:43Z","timestamp":1776754303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ADAMTS2 Modulates Inflammation, Autophagy, and Barrier Integrity Through PI3K\/AKT\/mTOR Signaling in LPS\u2010Induced Acute Respiratory Distress Syndrome"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-7637","authenticated-orcid":false,"given":"Song","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Intensive Care Unit Xishan People's Hospital of Wuxi City (Wuxi Branch of Zhongda Hospital Southeast University) Wuxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Xishan People's Hospital of Wuxi City (Wuxi Branch of Zhongda Hospital Southeast University) Wuxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youhong","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Xishan People's Hospital of Wuxi City (Wuxi Branch of Zhongda Hospital Southeast University) Wuxi 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