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Kidney Week

Abstract: TH-PO100

MAVS Modulates Inflammation and Apoptosis in Renal Ischemia-Reperfusion Injury

Session Information

  • AKI: Mechanisms - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Minami, Taichiro, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
  • Iwata, Yasunori, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
  • Kitajima, Shinji, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
  • Toyama, Tadashi, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
  • Hara, Akinori, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
  • Sakai, Norihiko, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
  • Shimizu, Miho, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
  • Wada, Takashi, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
Background

Mitochondria have a central role not only in the initiation of ischemia-reperfusion injury (IRI) but also are involved in recovery processes. Mitochondrial antiviral-signaling protein (MAVS) is a component of innate immunity, leading to cytokines production upon activation. Here, we characterize the role of MAVS in tubular epithelial cells during the various phases of IRI-induced AKI, and their relative importance to renal fibrogenesis.

Methods

We performed unilateral renal artery clamping for 50 minutes in wild-type mice (C57BL/6) and MAVS knockout mice and assessed the pathology at the acute kidney injury phase (Day2, Day5) and chronic phase (Day20).

Results

Compared with their wild-type counterparts, MAVS knockout mice showed less urine protein and tubular injury scores, tubular epithelial cell apoptosis in the acute stage of AKI, and attenuated fibrosis in the late stage. Immunostaining revealed that MAVS is mainly expressed in the renal tubules in the physiological state, and strongly expressed in the injured proximal tubules after renal ischemia-reperfusion. Transient transfection of MAVS in HEK293T cells increased TRAF6 expression, nuclear translocation of NFκB, and phosphorylation of MAPK (p38, ERK, JNK), suggesting that it activates inflammation and apoptosis. Moreover, MAVS inhibition resulted in less mitochondrial reactive oxygen species and pro-inflammatory cytokines production after hypoxia.

Conclusion

Collectively, we identify MAVS as a pro-inflammatory contributor to renal tubules in the early phase of AKI and it might be a therapeutic target.

Funding

  • NIDDK Support