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This study focused on ASXL1, a chromatin modifier regulating histone marks consisting of H3K27me3 (repressive) and H3K4me3 (activating) in M1 macrophages. We found that ASXL1\u2010positive M1 macrophages were significantly increased in the unilateral ischemia\u2013reperfusion injury kidneys of male mice in the acute phase. In cultured M1 macrophages, RNA sequencing revealed that\n                    <jats:italic>Asxl1<\/jats:italic>\n                    knockdown upregulated inflammatory response genes such as\n                    <jats:italic>Il6<\/jats:italic>\n                    and\n                    <jats:italic>Il1b<\/jats:italic>\n                    . Conversely, the expression of anti\u2010apoptotic genes\n                    <jats:italic>Csf3<\/jats:italic>\n                    and\n                    <jats:italic>Lcn2<\/jats:italic>\n                    was suppressed, and pathways related to interleukin\u201017 signaling and Fc\u03b3 receptor\u2010dependent phagocytosis were downregulated. In co\u2010culture experiments,\n                    <jats:italic>Asxl1<\/jats:italic>\n                    silencing in M1 macrophages induced more severe apoptosis and reduced proliferation of mouse renal cortical tubular cells. Mechanistically, chromatin immunoprecipitation analysis demonstrated that\n                    <jats:italic>Asxl1<\/jats:italic>\n                    knockdown significantly decreased H3K27me3 levels at the\n                    <jats:italic>Il6<\/jats:italic>\n                    and\n                    <jats:italic>Il1b<\/jats:italic>\n                    promoter regions and H3K4me3 levels at the\n                    <jats:italic>Csf3<\/jats:italic>\n                    and\n                    <jats:italic>Lcn2<\/jats:italic>\n                    promoter regions in M1 macrophages. These findings indicate that ASXL1 suppresses excessive inflammatory cytokine expression and preserves anti\u2010apoptotic activity through histone modifications, while maintaining phagocytic capacity in M1 macrophages. ASXL1 in M1 macrophages thus attenuates inflammatory activation and macrophage\u2010mediated renal tubular cell damage in AKI.\n                  <\/jats:p>","DOI":"10.14814\/phy2.71119","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:57:29Z","timestamp":1790830649000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ASXL1 in proinflammatory macrophages attenuates inflammatory activation and macrophage\u2010mediated renal tubular epithelial cell damage in acute kidney injury"],"prefix":"10.14814","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5844-7053","authenticated-orcid":false,"given":"Yoshiyasu","family":"Ogura","sequence":"first","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehito","family":"Sugasawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Medicine, and the Department of Sports Medicine Analysis, Research Facility Center for Science and Technology University of Tsukuba  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaomi","family":"Nangaku","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"},{"name":"Organ Pathophysiology Program The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-5127","authenticated-orcid":false,"given":"Imari","family":"Mimura","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine  Tokyo Japan"},{"name":"Organ Pathophysiology Program The University of Tokyo Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.06.032"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI190736"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03084-7"},{"key":"e_1_2_10_5_1","first-page":"373","article-title":"Fc receptor\u2010dependent mechanisms of monoclonal antibody therapy of cancer","volume":"382","author":"Bakema J. 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