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Yes\u2010associated protein (YAP1) is a key protein in the Hippo\u2013YAP1 signaling pathway and is involved in macrophage polarization. We aimed to determine the role of YAP1 in pulmonary inflammation following ALI and regulation of M1\/M2 polarization. Pulmonary inflammation and injury with upregulation of YAP1 were observed in lipopolysaccharide (LPS)\u2010induced ALI. The YAP1 inhibitor, verteporfin, attenuated pulmonary inflammation and improved lung function in ALI mice. Moreover, verteporfin promoted M2 polarization and inhibited M1 polarization in the lung tissues of ALI mice and LPS\u2010treated bone marrow\u2010derived macrophages (BMMs). Additionally, siRNA knockdown confirmed that silencing <jats:italic>Yap1<\/jats:italic> decreased chemokine ligand 2 (CCL2) expression and promoted M2 polarization, whereas silencing large tumor suppressor 1 (<jats:italic>Lats1<\/jats:italic>) increased CCL2 expression and induced M1 polarization in LPS\u2010treated BMMs. To investigate the role of inflammatory macrophages in ALI mice, we performed single\u2010cell RNA sequencing of macrophages isolated from the lungs. Thus, verteporfin could activate the immune\u2010inflammatory response, promote the potential of M2 macrophages, and alleviate LPS\u2010induced ALI. Our results reveal a novel mechanism where YAP1\u2010mediated M2 polarization alleviates ALI. Therefore, inhibition of YAP1 may be a target for the treatment of ALI.<\/jats:p>","DOI":"10.1002\/mco2.293","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T01:18:40Z","timestamp":1686187120000},"source":"Crossref","is-referenced-by-count":28,"title":["Inhibition of YAP1 activity ameliorates acute lung injury through promotion of M2 macrophage polarization"],"prefix":"10.1002","volume":"4","author":[{"given":"Lu","family":"Liang","sequence":"first","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target &amp; Clinical Pharmacology The State &amp; NMPA Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences &amp; The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of 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