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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
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Abstract titles should be brief and reflect the content of the abstract.
AKI is caused by various factors, including ischemia, infection, drugs, and aging, In AKI, the involvement of inflammatory macrophages (M1) is important in the progression of the disease. In this study, we aimed to elucidate the effect of AKI-induced M1 macrophages on the renal tubular cells from an epigenetic perspective. ASXL1, the histone modifier, regulates both H3K27me3, which suppresses gene expression, and H3K4me3, which activates gene expression. However, the role of ASXL1 in M1 macrophages in AKI is unknown.
We evaluated the ASXL1 expression of macrophages in kidneys in the acute phase of rat unilateral ischemia reperfusion injury (uIRI) model by immunostaining. In vitro, cultured macrophages RAW 264.7 were differentiated into M1 by stimulation with LPS, and we knocked down the expression of Asxl1 in RAW 264.7 by siRNA. Downstream genes regulated by Asxl1 in M1 macrophages were identified by RNA-seq. And, mouse tubular cells were co-cultured with the medium of M1 macrophages whose Asxl1 was knocked down, then evaluated the cytotoxicity and apoptosis of mouse renal tubular cells. Moreover, we performed chromatin immunoprecipitation (ChIP) using histone modification antibodies in order to clarify the epigenetic role of Asxl1 in M1 macrophages.
ASXL1 positive macrophages infiltrated the tubulointerstitium significantly in uIRI kidney. In vitro, by RNA-seq of RAW 264.7 cells, we identified 229 genes whose expression was further increased by knocking down of Asxl1. Gene ontology analysis revealed that pathways such as responses to viruses and innate immune responses were further upregulated by knocking down Asxl1 in M1 macrophages. And these pathways commonly contained inflammatory genes such as Il6 and Il1b. On the other hand, we also identified 283 genes whose expression was increased by LPS stimulation and decreased by knocking down of Asxl1. Gene ontology analysis revealed that the IL17 signaling pathway, which is involved in host defense against microorganisms and inflammatory diseases, were downregulated by knocking down Asxl1 in M1 macrophages. In this pathway, Csf3 and Lcn2, which have been reported to have anti-apoptotic and renal protective effects on tubular cells, were included. In the co-culture experiment, knockdown of Asxl1 in M1 macrophages enhanced cytotoxicity and apoptosis of mouse tubular cells. Besides, ChIP analysis showed that the H3K27me3 levels in the promoter regions of the inflammatory cytokines (Il6 and Il1b) were suppressed in M1 macrophages and knockdown of Asxl1 further suppressed the H3K27me3 levels in the same regions. In addition, in M1 macrophages, the H3K4me3 levels in the promoter regions of Csf3 and Lcn2 were increased by LPS administration, and knockdown of Asxl1 reduced the H3K4me3 levels of the same regions.
This study is the first research to reveal the epigenetic molecular mechanism in macrophages by which ASXL1 protects the kidney in the phase of AKI. In M1 macrophages, ASXL1 suppresses the excessive expression of inflammation-related genes (Il6, Il1b) by regulating H3K27me3, and promotes the expression of anti-apoptosis-related genes (Csf3, Lcn2) by regulating H3K4me3.
