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Our previous data showed that electroporation\u2010mediated 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\u2010induced ALI in mice. More importantly, our recent publication showed that gene delivery of MRCK\u03b1, the downstream effector of \u03b21 subunit-mediated signaling towards upregulation of adhesive junctions and epithelial and endothelial barrier integrity, also provided therapeutic potential for ARDS treatment in vivo but without necessarily accelerating AFC, indicating that for ARDS treatment, improving alveolar capillary barrier function may be of more benefit than improving fluid clearance. In the present study, we investigated the therapeutical potential of \u03b22 and \u03b23 subunits, the other two \u03b2 isoforms of Na\n                    <jats:sup>+<\/jats:sup>\n                    , K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase, for LPS\u2010induced ALI. We found that gene transfer of either the \u03b21, \u03b22, or \u03b23 subunits significantly increased AFC compared to the basal level in na\u00efve animals and each gave similar increased AFC to each other. However, unlike that of the \u03b21 subunit, gene transfer of the \u03b22 or \u03b23 subunit into pre-injured animal lungs failed to show the beneficial effects of attenuated histological damage, neutrophil infiltration, overall lung edema, or increased lung permeability, indicating that \u03b22 or \u03b23 gene delivery could not treat LPS induced lung injury. Further, while \u03b21 gene transfer increased levels of key tight junction proteins in the lungs of injured mice, that of either the \u03b22 or \u03b23 subunit had no effect on levels of tight junction proteins. Taken together, this strongly suggests that restoration of alveolar-capillary barrier function alone may be of equal or even more benefit than improving AFC for ALI\/ARDS treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41598-023-33985-4","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T06:03:54Z","timestamp":1682489034000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Upregulation of alveolar fluid clearance is not sufficient for Na+,K+-ATPase \u03b2 subunit-mediated gene therapy of LPS-induced acute lung injury in mice"],"prefix":"10.1038","volume":"13","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian M.","family":"Schiralli-Lester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Norman","sequence":"additional","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":[[2023,4,26]]},"reference":[{"issue":"1","key":"33985_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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