Skip to content
DraconiticResearch
Search Sources API
223,421 studies31 sourcesUpdated 54 min ago
Peer-reviewedCC BY 4.0Physiological Reports

ASXL1 in proinflammatory macrophages attenuates inflammatory activation and macrophage‐mediated renal tubular epithelial cell damage in acute kidney injury

  • Yoshiyasu Ogura1
  • Takehito Sugasawa2
  • Masaomi Nangaku1,3
  • Imari Mimura1,3
  1. 1Division of Nephrology and Endocrinology The University of Tokyo Graduate School of Medicine Tokyo Japan
  2. 2Department 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
  3. 3Organ Pathophysiology Program The University of Tokyo Graduate School of Medicine Tokyo Japan
Read full textPDFDOICite

Abstract

Macrophages are major contributors to inflammatory responses in acute kidney injury (AKI) and rapidly alter their gene expression through epigenetic regulation. 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‐positive M1 macrophages were significantly increased in the unilateral ischemia–reperfusion injury kidneys of male mice in the acute phase. In cultured M1 macrophages, RNA sequencing revealed that Asxl1 knockdown upregulated inflammatory response genes such as Il6 and Il1b. Conversely, the expression of anti‐apoptotic genes Csf3 and Lcn2 was suppressed, and pathways related to interleukin‐17 signaling and Fcγ receptor‐dependent phagocytosis were downregulated. In co‐culture experiments, Asxl1 silencing in M1 macrophages induced more severe apoptosis and reduced proliferation of mouse renal cortical tubular cells. Mechanistically, chromatin immunoprecipitation analysis demonstrated that Asxl1 knockdown significantly decreased H3K27me3 levels at the Il6 and Il1b promoter regions and H3K4me3 levels at the Csf3 and Lcn2 promoter regions in M1 macrophages. These findings indicate that ASXL1 suppresses excessive inflammatory cytokine expression and preserves anti‐apoptotic activity through histone modifications, while maintaining phagocytic capacity in M1 macrophages. ASXL1 in M1 macrophages thus attenuates inflammatory activation and macrophage‐mediated renal tubular cell damage in AKI.

Related

  1. Itaconate as the endogenous brake of proinflammatory macrophage activation alleviates inflammation in liver fibrogenesis.
    Kai Zhang, Tong Li, Wenhui Liu +4
    Hepatology communicationsPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMC
  2. Gossypetin Attenuates Concanavalin A-Induced Inflammatory Responses in Macrophages in vitro by Suppressing Oxidative Stress and p38 MAPK/NF-κB Signaling
    Soyeon Jang, Jiwon Ko, Hyejin Hyung +9
    Journal of Inflammation ResearchPeer-reviewedCC BY-NC 4.0Full textPharmacology & toxicologyPMCEurope PMC
  3. SIK2 antagonizes postinfarction cardiac repair by driving macrophage proinflammatory and impairing efferocytosis
    Wu-Wei Rong, Zi-Qi Xu, Shuai Shao +13
    Science AdvancesPeer-reviewedCC BYFull textCardiovascular medicineCrossrefEurope PMC
  4. Maternal nonylphenol exposure induces offspring intestinal injury and enteric neuronal defects involving proinflammatory macrophage polarization
    Xuefeng Yang, Lu Huang, Yan Qu +5
    Scientific ReportsPeer-reviewedCC BYFull text1 citedSurgery & anaesthesiaDOAJ
  5. Targeting PDE2A of macrophages attenuates sorafe​nib-induced cardiotoxicity
    Sijia Li, Shuangli Zhu, Kai Fu +7
    BMC MedicinePeer-reviewedCC BY 4.0General medicineCrossref

Cite

BibTeXRIS
BibTeX
@article{ogura2026asxl1,
  title = {{ASXL1 in proinflammatory macrophages attenuates inflammatory activation and macrophage‐mediated renal tubular epithelial cell damage in acute kidney injury}},
  author = {Yoshiyasu Ogura and Takehito Sugasawa and Masaomi Nangaku and Imari Mimura},
  journal = {Physiological Reports},
  year = {2026},
  month = sep,
  doi = {10.14814/phy2.71119},
  url = {https://doi.org/10.14814/phy2.71119},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - ASXL1 in proinflammatory macrophages attenuates inflammatory activation and macrophage‐mediated renal tubular epithelial cell damage in acute kidney injury
AU  - Yoshiyasu Ogura
AU  - Takehito Sugasawa
AU  - Masaomi Nangaku
AU  - Imari Mimura
PY  - 2026
DA  - 2026/09/30
JO  - Physiological Reports
DO  - 10.14814/phy2.71119
UR  - https://doi.org/10.14814/phy2.71119
AB  - Macrophages are major contributors to inflammatory responses in acute kidney injury (AKI) and rapidly alter their gene expression through epigenetic regulation. 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‐positive M1 macrophages were significantly increased in the unilateral ischemia–reperfusion injury kidneys of male mice in the acute phase. In cultured M1 macrophages, RNA sequencing revealed that Asxl1 knockdown upregulated inflammatory response genes such as Il6 and Il1b. Conversely, the expression of anti‐apoptotic genes Csf3 and Lcn2 was suppressed, and pathways related to interleukin‐17 signaling and Fcγ receptor‐dependent phagocytosis were downregulated. In co‐culture experiments, Asxl1 silencing in M1 macrophages induced more severe apoptosis and reduced proliferation of mouse renal cortical tubular cells. Mechanistically, chromatin immunoprecipitation analysis demonstrated that Asxl1 knockdown significantly decreased H3K27me3 levels at the Il6 and Il1b promoter regions and H3K4me3 levels at the Csf3 and Lcn2 promoter regions in M1 macrophages. These findings indicate that ASXL1 suppresses excessive inflammatory cytokine expression and preserves anti‐apoptotic activity through histone modifications, while maintaining phagocytic capacity in M1 macrophages. ASXL1 in M1 macrophages thus attenuates inflammatory activation and macrophage‐mediated renal tubular cell damage in AKI.
SN  - 2051-817X
ER  -