{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:52:04Z","timestamp":1778277124674,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T00:00:00Z","timestamp":1633737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK079307"],"award-info":[{"award-number":["DK079307"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK084005"],"award-info":[{"award-number":["DK084005"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK061296"],"award-info":[{"award-number":["DK061296"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK007052"],"award-info":[{"award-number":["DK007052"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["HL147818"],"award-info":[{"award-number":["HL147818"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Society of 408 Nephrology","award":["Carl W. Gottschalk Research Scholar Award"],"award-info":[{"award-number":["Carl W. Gottschalk Research Scholar Award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute kidney injury due to renal ischemia-reperfusion injury (IRI) may lead to chronic or end stage kidney disease. A greater understanding of the cellular mechanisms underlying IRI are required to develop therapeutic options aimed at limiting or reversing damage from IRI. Prior work has shown that deletion of the \u03b1 subunit of the epithelial Na+ channel (ENaC) in endothelial cells protects from IRI by increasing the availability of nitric oxide. While canonical ENaCs consist of an \u03b1, \u03b2, and \u03b3 subunit, there is evidence of non-canonical ENaC expression in endothelial cells involving the \u03b1 subunit. We therefore tested whether the deletion of the \u03b3 subunit of ENaC also protects mice from IRI to differentiate between these channel configurations. Mice with endothelial-specific deletion of the \u03b3 subunit and control littermates were subjected to unilateral renal artery occlusion followed by 48 h of reperfusion. No significant difference was noted in injury between the two groups as assessed by serum creatinine and blood urea nitrogen, levels of specific kidney injury markers, and histological examination. While deletion of the \u03b3 subunit did not alter infiltration of immune cells or cytokine message, it was associated with an increase in levels of total and phosphorylated endothelial nitric oxide synthase (eNOS) in the injured kidneys. Our studies demonstrate that even though deletion of the \u03b3 subunit of ENaC may allow for greater activation of eNOS, this is not sufficient to prevent IRI, suggesting the protective effects of \u03b1 subunit deletion may be due, in part, to other mechanisms.<\/jats:p>","DOI":"10.3390\/ijms222010914","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:23:25Z","timestamp":1633901005000},"page":"10914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Deletion of the Gamma Subunit of ENaC in Endothelial Cells Does Not Protect against Renal Ischemia Reperfusion Injury"],"prefix":"10.3390","volume":"22","author":[{"given":"Stephanie M.","family":"Mutchler","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahpara","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald E.","family":"Kohan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-5415","authenticated-orcid":false,"given":"Thomas R.","family":"Kleyman","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Cell Biology, and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roderick J.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.23876\/j.krcp.19.062","article-title":"Mechanisms and therapeutic targets of ischemic acute kidney injury","volume":"38","author":"Han","year":"2019","journal-title":"Kidney Res. 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