{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:23:32Z","timestamp":1787016212960,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973404"],"award-info":[{"award-number":["81973404"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2022\u2010MS\u2010224"],"award-info":[{"award-number":["2022\u2010MS\u2010224"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"\n Abstract<\/jats:title>\n \n Long\u2010term abuse of methamphetamine (MA) can cause lung toxicity. Intercellular communication between macrophages and alveolar epithelial cells (AECs) is critical for maintaining lung homeostasis. Microvesicles (MVs) are an important medium of intercellular communication. However, the mechanism of macrophage MVs (MMVs) in MA\u2010induced chronic lung injury remains unclear. This study aimed to investigate if MA can augment the activity of MMVs and if circ_YTHDF2 is a key factor in MMV\u2010mediated macrophage\u2013AEC communication, and to explore the mechanism of MMV\u2010derived circ_YTHDF2 in MA\u2010induced chronic lung injury. MA elevated peak velocity of the pulmonary artery and pulmonary artery accelerate time, reduced the number of alveolar sacs, thickened the alveolar septum, and accelerated the release of MMVs and the uptake of MMVs by AECs. Circ_YTHDF2 was downregulated in lung and MMVs induced by MA. The immune factors in MMVs were increased by si\u2010circ_YTHDF. Circ_YTHDF2 knockdown in MMVs induced inflammation and remodelling in the internalised AECs by MMVs, which was reversed by circ_YTHDF2 overexpression in MMVs. Circ_YTHDF2 bound specifically to and sponged miRNA\u2010145\u20105p. Runt\u2010related transcription factor 3 (\n RUNX3<\/jats:italic>\n ) was identified as potential target of miR\u2010145\u20105p. RUNX3 targeted zinc finger E\u2010box\u2010binding homeobox 1 (\n ZEB1<\/jats:italic>\n )\u2010related inflammation and EMT of AECs.\n In vivo<\/jats:italic>\n , circ_YTHDF2 overexpression\u2010MMVs attenuated MA\u2010induced lung inflammation and remodelling by the circ_YTHDF2\u2013miRNA\u2010145\u20105p\u2013RUNX3 axis. Therefore, MA abuse can induce pulmonary dysfunction and alveolus injury. The immunoactivity of MMVs is regulated by circ_YTHDF2. Circ_YTHDF2 in MMVs is the key to communication between macrophages and AECs. Circ_YTHDF2\u00a0sponges miR\u2010145\u20105p targeting\n RUNX3<\/jats:italic>\n to participate in\n ZEB1<\/jats:italic>\n \u2010related inflammation and remodelling of AECs. MMV\u2010derived circ_YTHDF2 would be an important therapeutic target for MA\u2010induced chronic lung injury.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Methamphetamine (MA) abuse induces pulmonary dysfunction and alveoli injury.<\/jats:p>\n <\/jats:list-item>\n \n The immunoactivity of macrophage microvesicles (MMVs) is regulated by circ_YTHDF2.<\/jats:p>\n <\/jats:list-item>\n \n Circ_YTHDF2 in MMVs is the key to MMV\u2010mediated intercellular communication between macrophages and alveolar epithelial cells.<\/jats:p>\n <\/jats:list-item>\n \n \n Circ_YTHDF2\u00a0sponges miR\u2010145\u20105p targeting runt\u2010related transcription factor 3 (\n RUNX3<\/jats:italic>\n ) to participate in zinc finger E\u2010box\u2010binding homeobox 1 (\n ZEB1<\/jats:italic>\n )\u2010related inflammation and remodelling.\n <\/jats:p>\n <\/jats:list-item>\n \n MMV\u2010derived circ_YTHDF2 would be an important therapeutic target for MA\u2010induced chronic lung injury.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp284086","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T04:54:31Z","timestamp":1681966471000},"page":"5107-5128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Macrophage microvesicle\u2010derived circ_YTHDF2 in methamphetamine\u2010induced chronic lung injury"],"prefix":"10.1113","volume":"601","author":[{"given":"Lei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy China Medical University Shenyang Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Jian","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy China Medical University Shenyang 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