Kidney Week

Abstract: TH-PO0676

Endogenous Cellular RNA Drives Sterile Kidney Inflammation Through the RIG-I/MAVS Pathway

Session Information

• AKI: Mechanisms - Inflammation and Repair
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Minami, Taichiro, Kanazawa Daigaku, Kanazawa, Ishikawa Prefecture, Japan

Taichiro Minami, DrMed

• Oshima, Megumi, Kanazawa Daigaku, Kanazawa, Ishikawa Prefecture, Japan

Megumi Oshima, MD, PhD

• Yamamura, Yuta, Kanazawa Daigaku, Kanazawa, Ishikawa Prefecture, Japan

Yuta Yamamura, MD

• Ito, Kiyoaki, Kanazawa Daigaku, Kanazawa, Ishikawa Prefecture, Japan

Kiyoaki Ito, MD, PhD

• Sakai, Norihiko, Kanazawa Daigaku, Kanazawa, Ishikawa Prefecture, Japan

Norihiko Sakai, MD, PhD

• Shimizu, Miho, Kanazawa Daigaku, Kanazawa, Ishikawa Prefecture, Japan

Miho Shimizu, MD, PhD

• Wada, Takashi, Kanazawa Daigaku, Kanazawa, Ishikawa Prefecture, Japan

Takashi Wada, MD, PhD

• Iwata, Yasunori, Kanazawa Daigaku, Kanazawa, Ishikawa Prefecture, Japan

Yasunori Iwata, MD, PhD

Background

Acute kidney injury (AKI) is characterized by sterile inflammation triggered by endogenous danger-associated molecular patterns (DAMPs), yet the mechanisms linking tissue injury to innate immune activation remain incompletely understood. Retinoic acid–inducible gene I (RIG-I) is a cytosolic RNA sensor that activates mitochondrial antiviral-signaling protein (MAVS), a central adaptor of innate immune signaling. Although the RIG-I/MAVS pathway is essential for antiviral immunity, its role in sterile kidney injury remains unclear. We investigated whether cellular RNA released during ischemic injury functions as a pathogenic DAMP that exacerbates AKI through the RIG-I/MAVS pathway.

Methods

Renal ischemia-reperfusion (I/R) injury was induced in wild-type and MAVS-deficient mice. A pharmacologic RIG-I inhibitor was administered to evaluate therapeutic targeting of upstream RNA sensing. Oxidatively stressed tubular epithelial cell (TEC)-derived RNA and injured kidney-derived RNA were analyzed in vitro and in vivo. Fluorescently labeled cellular RNA was intravenously injected to assess renal tubular uptake. Inflammatory signaling, apoptosis, and downstream pathway activation were evaluated by immunostaining, WB, and quantitative PCR. Human kidney transplant biopsy samples were analyzed for clinical relevance.

Results

Renal I/R injury induced marked upregulation of RIG-I and MAVS in proximal TECs. MAVS deficiency attenuated tubular injury, inflammatory cytokine expression, apoptosis, and fibrosis. Oxidative stress generated immunostimulatory cellular RNA that robustly activated MAVS signaling, whereas cellular DNA had minimal effects. Intravenously administered cellular RNA was internalized by TECs and amplified renal inflammation in a MAVS-dependent manner. Mechanistically, MAVS activation promoted TRAF6-dependent NF-κB and p38 MAPK signaling, resulting in enhanced IFN-β production and tubular injury. Pharmacologic inhibition of RIG-I similarly reduced renal inflammation and tissue injury after I/R. In human kidney transplant biopsies, increased intrarenal MAVS expression correlated with subsequent renal functional decline.

Conclusion

Endogenous cellular RNA functions as a pathogenic DAMP that activates the RIG-I/MAVS pathway and amplifies sterile inflammation in AKI. These findings identify MAVS-dependent RNA sensing as a potential therapeutic target and mechanistic driver of ischemic kidney injury.

Acknowledgment

This work was supported by JSPS KAKENHI Grant Number JP 24K11406.

Funding

• Government Support – Non-U.S.