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Enhancing AFC has long been considered one of the primary therapeutic goals in gene therapy treatments for ARDS. We previously showed that electroporation-mediated gene delivery of the Na\n                    <jats:sup>+<\/jats:sup>\n                    , K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase \u03b21 subunit not only increased AFC, but also restored alveolar barrier function through upregulation of tight junction proteins, leading to treatment of LPS-induced ALI in mice. We identified MRCK\u03b1 as an interaction partner of \u03b21 which mediates this upregulation in cultured alveolar epithelial cells. In this study, we investigate whether electroporation-mediated gene transfer of MRCK\u03b1 to the lungs can attenuate LPS-induced acute lung injury in vivo. Compared to mice that received a non-expressing plasmid, those receiving the MRCK\u03b1 plasmid showed attenuated LPS-increased pulmonary edema and lung leakage, restored tight junction protein expression, and improved overall outcomes. Interestingly, gene transfer of MRCK\u03b1 did not alter AFC rates. Studies using both cultured microvascular endothelial cells and mice suggest that \u03b21 and MRCK\u03b1 upregulate junctional complexes in both alveolar epithelial and capillary endothelial cells, and that one or both barriers may be positively affected by our approach. Our data support a model of treatment for ALI\/ARDS in which improvement of alveolar-capillary barrier function alone may be of more benefit than improvement of alveolar fluid clearance.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-99897-3","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T06:04:42Z","timestamp":1634796282000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Gene transfer of MRCK\u03b1 rescues lipopolysaccharide-induced acute lung injury by restoring alveolar capillary barrier function"],"prefix":"10.1038","volume":"11","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Dean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"99897_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41572-019-0069-0","volume":"5","author":"MA Matthay","year":"2019","unstructured":"Matthay, M. 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