{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:11:53Z","timestamp":1789924313640,"version":"4.0.1"},"reference-count":80,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"DHAC | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1172929"],"award-info":[{"award-number":["1172929"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Independent Research Institutes Infrastructure Support Scheme","award":["9000719"],"award-info":[{"award-number":["9000719"]}]},{"name":"Victoria Government Operational Infrastructure Support Scheme"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,22]]},"abstract":"<jats:p>Ischemia-reperfusion injury (IRI) occurs when the blood supply to an organ is temporarily reduced and then restored. Kidney IRI is a form of acute kidney injury (AKI), which often progresses to kidney fibrosis. Necroptosis is a regulated necrosis pathway that has been implicated in kidney IRI. Necroptotic cell death involves the recruitment of the RIPK1 and RIPK3 kinases and the activation of the terminal effector, the mixed lineage kinase domain-like (MLKL) pseudokinase. Phosphorylated MLKL causes cell death by plasma membrane rupture, driving \u2018necroinflammation\u2019. Owing to their apical role in the pathway, RIPK1 and RIPK3 have been implicated in the development of kidney fibrosis. Here, we used a mouse model of unilateral kidney IRI to assess whether the inhibition of RIPK1 or RIPK3 kinase activity reduces AKI and the progression to kidney fibrosis. Mice treated with the RIPK1 inhibitor Nec-1s, either before or after IR, showed reduced kidney injury at 24 hr compared with controls, whereas no protection was offered by the RIPK3 inhibitor GSK\u00b4872. In contrast, treatment with either inhibitor from days 3 to 9 post-IR reduced the degree of kidney fibrosis at day 28. These findings further support the role of necroptosis in IRI and provide important validation for the contribution of both RIPK1 and RIPK3 catalytic activities in the progression of kidney fibrosis. Targeting the necroptosis pathway could be a promising therapeutic strategy to mitigate kidney disease following IR.<\/jats:p>","DOI":"10.1042\/bcj20240569","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T16:20:56Z","timestamp":1734711656000},"page":"73-86","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of RIPK1 or RIPK3 kinase activity post ischemia-reperfusion reduces the development of chronic kidney injury"],"prefix":"10.1042","volume":"482","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5422-0856","authenticated-orcid":false,"given":"Aspasia","family":"Pefanis","sequence":"first","affiliation":[{"name":"1Immunology Research Centre, St Vincent\u2019s Hospital, Melbourne, Victoria, Australia"},{"name":"2Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"3Department of Nephrology, St Vincent\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2312-0374","authenticated-orcid":false,"given":"Anjan K.","family":"Bongoni","sequence":"additional","affiliation":[{"name":"1Immunology Research Centre, St Vincent\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1626-1905","authenticated-orcid":false,"given":"Jennifer L.","family":"McRae","sequence":"additional","affiliation":[{"name":"1Immunology Research Centre, St Vincent\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-0743","authenticated-orcid":false,"given":"Evelyn J.","family":"Salvaris","sequence":"additional","affiliation":[{"name":"1Immunology Research Centre, St Vincent\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-9019","authenticated-orcid":false,"given":"Nella","family":"Fisicaro","sequence":"additional","affiliation":[{"name":"1Immunology Research Centre, St Vincent\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0195-3949","authenticated-orcid":false,"given":"James M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"4Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia"},{"name":"5Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"6Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-4952","authenticated-orcid":false,"given":"Francesco L.","family":"Ierino","sequence":"additional","affiliation":[{"name":"2Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"3Department of Nephrology, St Vincent\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9016-4954","authenticated-orcid":false,"given":"Peter J.","family":"Cowan","sequence":"additional","affiliation":[{"name":"1Immunology Research Centre, St Vincent\u2019s Hospital, Melbourne, Victoria, Australia"},{"name":"2Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"2025020309305262400_BCJ-2024-0569C1","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1172\/JCI45161","article-title":"Cellular pathophysiology of ischemic acute kidney injury","volume":"121","author":"Bonventre","year":"2011","journal-title":"J. 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