{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:30:29Z","timestamp":1793212229654,"version":"4.5.0"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Candian Institutes of Health Research","award":["Project Grant"],"award-info":[{"award-number":["Project Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,22]]},"abstract":"<jats:p>Nonresolving inflammation and maladaptive renal repair contribute to the pathogenesis of acute kidney injury (AKI) transition to chronic kidney disease (CKD). Few therapies have been identified that can modulate these injurious pathways following AKI. Spleen tyrosine kinase (SYK) is an immune regulator expressed in the kidney and a potential therapeutic target for AKI. The effect of the selective SYK inhibitor entospletinib was studied in AKI-to-CKD transition. Entospletinib was administered to mice undergoing unilateral renal ischemia-reperfusion injury (IRI), with kidneys analyzed over 14 days. Single-cell RNA sequencing, digital spatial profiling, intravital microscopy, and flow cytometry were employed to study renal phenotypes. Entospletinib administered before and after IRI protected ischemic kidneys and significantly attenuated the transition to CKD. Entospletinib targeted leukocyte-expressed SYK and prevented neutrophil\/monocyte recruitment to the kidney. Entospletinib reduced nonresolving tubulointerstitial inflammation after AKI by blocking activation of mannose receptor-1\u2013 and C-type lectin domain family 7 member A\u2013expressing proinflammatory macrophages. The resolution of renal inflammation mediated by entospletinib was associated with a reciprocal increase in resident macrophages, reparative gene expression, preserved tubular integrity, and reduced renal fibrosis. The SYK inhibitor entospletinib resolves renal inflammation and promotes repair following AKI.<\/jats:p>","DOI":"10.1172\/jci.insight.189601","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T18:24:22Z","timestamp":1756232662000},"source":"Crossref","is-referenced-by-count":8,"title":["The spleen tyrosine kinase inhibitor entospletinib resolves inflammation to promote repair following acute kidney injury"],"prefix":"10.1172","volume":"10","author":[{"given":"Esteban E.","family":"Elias","sequence":"first","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisay Getie","family":"Belay","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Derakhshani","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela","family":"Andonegui","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig N.","family":"Jenne","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-4188","authenticated-orcid":true,"given":"Antoine","family":"Dufour","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan A.","family":"Bracey","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3820-7192","authenticated-orcid":true,"given":"Justin","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Muruve","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2013.282"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32563-2"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2012.280"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31772-9"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2005477117"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32634-0"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51186-z"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0247-z"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.379"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017101069"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.130651"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009060615"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.10.008"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00752-7"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0110-2"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81166"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114359"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017080863"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.04.013"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04131-7"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39087"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021121548"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192230"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.119"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm0142"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2012.1"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nri2765"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2022.2131751"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2018.05.022"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.04.007"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102603"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2021.12.003"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2020.34.s1.07539"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.10.020"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2016.01.023"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1021\/jm500228a"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-016-0476-x"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V94632"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-259556"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.03.039"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1136\/mp.52.4.189"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211314"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001829"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0953-0"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79590"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.129"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-10-56"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425616"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-56"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.005"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.765034"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2015.09.004"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-595934"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34780"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019040337"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2024.116911"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20188746"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01206-w"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0292-x"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0472-9"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz931"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/189601\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T15:08:26Z","timestamp":1779030506000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/189601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":64,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8,22]]},"published-print":{"date-parts":[[2025,8,22]]}},"alternative-id":["10.1172\/jci.insight.189601"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.189601","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]},"article-number":"e189601"}}