{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:03:19Z","timestamp":1790053399807,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2024A1515012914"],"award-info":[{"award-number":["2024A1515012914"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Acute lung injury\/acute respiratory distress syndrome (ALI\/ARDS), a common complication of sepsis, is critically characterized by disruption of the alveolar\u2013capillary barrier. The use of mesenchymal stem cells (MSCs) has emerged as a promising therapeutic strategy for ARDS owing to their potent paracrine effects. Wingless-type MMTV integration site family member 5A(Wnt5a) is a secreted protein with context-dependent effects on angiogenesis. This study aimed to investigate whether Wnt5a contributes to bone marrow-derived MSC (BMSC)-mediated repair of endothelial injury and whether Wnt5a-overexpressing BMSCs improve outcomes in an ALI animal model. Methods: Lipopolysaccharide (LPS) was used to induce endothelial cell (ECs) injury in vitro. EC proliferation, migration, tube formation and permeability, together with the expression of the junctional proteins zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) and the apoptosis-related proteins Bax and Bcl-2, were assessed after coculture with genetically modified BMSCs. In vivo, ALI was induced in mice by intraperitoneal administration of LPS. Lung histopathology, the lung wet-to-dry weight ratio, cytokine concentrations in bronchoalveolar lavage fluid (BALF) and serum, Evans blue extravasation, and the expression of junctional and apoptosis-related proteins were evaluated. PI3K\/AKT signaling was examined as a potential pathway associated with the observed effects. Results: Compared with the vector-BMSCs, Wnt5a-overexpressing BMSCs increased the proliferation, migration, and tube formation of LPS-injured ECs; reduced endothelial permeability; preserved junctional protein expression; and shifted apoptosis-related protein expression towards an anti-apoptotic profile. Wnt5a knockdown attenuated these responses. In vivo, treatment with Wnt5a-overexpressing BMSCs was associated with less histological lung injury, lower inflammatory cytokine concentrations and a similar shift in apoptosis-related protein expression after LPS challenge. These protective effects were accompanied by enhanced PI3K\/AKT signaling. Conclusions: Wnt5a overexpression optimized the protective effects of BMSCs against ALI in vivo and protected against LPS-induced EC barrier dysfunction in vitro, accompanied by enhanced PI3K\/AKT signaling.<\/jats:p>","DOI":"10.3390\/biom16091356","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Effects of Wnt5a-Overexpressing Bone Marrow Mesenchymal Stem Cells on Endothelial Barrier Repair in Acute Lung Injury"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1351-8362","authenticated-orcid":false,"given":"Shiqi","family":"Li","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Institute of Respiratory Diseases, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanmei","family":"He","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Institute of Respiratory Diseases, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manliang","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Institute of Respiratory Diseases, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintong","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Institute of Respiratory Diseases, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-902X","authenticated-orcid":false,"given":"Mian","family":"Zeng","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China"},{"name":"Institute of Respiratory Diseases, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sun, B., Lei, M., Zhang, J., Kang, H., Liu, H., and Zhou, F. 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