ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Abstract: TH-PO090

Double-Stranded DNA-Induced AIM2 Pyroptosis Limits Excessive Inflammation During Rhabdomyolysis-Induced AKI

Session Information

  • AKI: Mechanisms - I
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Baatarjav, Chintogtokh, Jichi Ika Daigaku, Shimotsuke, Tochigi, Japan
  • Komada, Takanori, Jichi Ika Daigaku, Shimotsuke, Tochigi, Japan
  • Takahashi, Masafumi, Jichi Ika Daigaku, Shimotsuke, Tochigi, Japan

Rhabdomyolysis-induced acute kidney injury (RIAKI) is a severe complication of rhabdomyolysis, reportedly in part via double-stranded DNA (dsDNA) released from necrotic muscle. A dsDNA-sensor absent in melanoma 2 (AIM2) engages inflammasome activation, leading to maturation of IL-1β and gasdermin D (GSDMD)-dependent pro-inflammatory cell death called pyroptosis. The role of AIM2-mediated pyroptosis during RIAKI remains unknown.


C57BL/6J-background wild type (WT) and Aim2-knockout (Aim2-KO) mice underwent intramuscular glycerol injection to induce RIAKI. Isolated kidney macrophages and bone marrow-derived macrophages were subjected to dsDNA-induced pyroptosis assays in vitro.


A specific endonuclease for dsDNA, DNase-I, effectively ameliorated tubular injury and inflammation during RIAKI, corroborating that dsDNA is a critical danger molecule of RIAKI. TUNEL staining and immunoblotting for GSDMD in RIAKI kidneys demonstrated massive macrophage pyroptosis in WT, and Aim2-KO diminished this response. While pyroptosis was suppressed, Aim2-KO kidneys displayed abnormally more macrophage accumulation than WT. Aim2-KO promoted RIAKI by TANK-binding kinase 1 (TBK1)-NF-κB signalling and recruited more CD206+CXCR3+ macrophages, resulting in excessive kidney inflammation, fibrosis, and sustained kidney dysfunction. In in vitro study, dsDNA induced swift pyroptotic cell death in kidney macrophages without releasing IL-1β. Aim2-KO macrophages were devoid of pyroptosis in response to dsDNA. These surviving Aim2-KO macrophages alternatively developed STING-TBK1-IRF3/NF-κB activation, and secreted IFNβ and TNFα. Conditioned medium of dsDNA-treated Aim2-KO macrophages, not WT macrophages, upregulated pro-inflammatory genes on macrophages and kidney tubular epithelial cells. These results indicate pro-inflammatory functions of Aim2-deficient macrophages escaped from pyroptosis.


Aim2 deficiency worsens inflammation and fibrosis of RIAKI despite reduced macrophage pyroptosis. Macrophage survivors lacking Aim2 potentiate inflammation on surrounding cells. dsDNA-induced, AIM2-dependent macrophage pyroptosis potentially provides a resolution of inflammation and determines the healing process of RIAKI.


  • Government Support – Non-U.S.