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Adv."],"published-print":{"date-parts":[[2026,8,28]]},"abstract":"<jats:p>\n                    Lytic cell death pathways drive hepatic ischemia-reperfusion injury (IRI). The transmembrane protein ninjurin-1 (NINJ1) aggregates in the plasma membrane to permeabilize the cell during multiple cell death pathways implicated in hepatic IRI. We hypothesized that NINJ1 mediates liver IRI and that its inhibition would mitigate injury. We found that NINJ1 is highly expressed in human liver tissue and that its up-regulation and activation correlate with early allograft dysfunction in liver transplant patients. Using a segmental hepatic IRI model in mice and rats,\n                    <jats:italic toggle=\"yes\">Ninj1<\/jats:italic>\n                    genetic deletion or pharmacologic inhibition diminished acute injury. Mice with hepatocyte- or macrophage-specific\n                    <jats:italic toggle=\"yes\">Ninj1<\/jats:italic>\n                    knockout had reduced hepatocellular injury following IRI, suggesting that NINJ1 within both populations contributes to the resulting liver injury. Mechanistically, we found that hepatocytes and Kupffer cells are susceptible to hypoxia-induced NINJ1-mediated plasma membrane rupture, which can be pharmacologically prevented. We therefore position NINJ1 as a potential new therapeutic target to limit hepatic IRI, with important implications for liver transplantation.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg9496","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:59:39Z","timestamp":1787767179000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Ninjurin-1 mediates hepatic ischemia-reperfusion injury"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-6467","authenticated-orcid":true,"given":"Jan","family":"Mossemann","sequence":"first","affiliation":[{"name":"Cell Biology Program, Hospital for Sick Children, Toronto, Canada."},{"name":"Department of General, Visceral, Thorax and Transplant Surgery, University Hospital of Cologne, Cologne, 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