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Kidney Week

Abstract: TH-PO006

Renal Protective Effect by Vagus Nerve Stimulation After Kidney Injury

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Uni, Rie, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
  • Inoue, Tsuyoshi, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
  • Surattichaiyakul, Bongkod, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
  • Peerapanyasut, Wachirasek, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
  • Hasegawa, Sho, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
  • Maekawa, Hiroshi, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
  • Nangaku, Masaomi, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
  • Inagi, Reiko, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
Background

We previously reported that the macrophages with vagus nerve stimulation (VNS) before bilateral ischemia-reperfusion injury (IRI) protect the kidney from the injury by activating the cholinergic anti-inflammatory pathway (CAP) in mice. Clinically, it would be more beneficial if VNS after injury could protect the kidney. We evaluated the effect of VNS after the injury both in vitro and in vivo model.

Methods

<LPS model> Both murine macrophage cell line RAW 264.7 and primary peritoneal macrophages were administered LPS (100 ng/ml). Human monocyte cell line U937 also received LPS (1 μg/ml). Because a7 nicotinic receptor plays an important role in the CAP, all of the cells were treated with a7nicotinic receptor agonist GTS-21 (50 mM for each) 4 and 6 hours after LPS administration, followed by assessment of the inflammatory status (TNF-α, IL-1β). In vivo, C57BL/6 mice were injected with LPS (5 mg/kg) intraperitoneally, and GTS-21 (10 mg/kg) was administered 4 and 6 hours later. Cytokine levels such as systemic TNF-α and splenic IL-1β and kidney injury markers such as Kim-1 were evaluated 8 hours after LPS administration. <IRI model> C57BL/6 mice underwent unilateral IRI (uniIRI). Followingly, VNS or sham stimulation was performed 3 times a week for 2 weeks, then the extent of kidney fibrosis (a-SMA, Masson's trichrome staining) was evaluated 2 weeks after the injury.

Results

GTS-21 decreased TNF-α expression level induced by LPS in macrophages /monocyte we used. In vivo, GTS-21 significantly suppressed LPS-induced kidney injury such as increased Kim-1 expression, as well as inflammation such as increased plasma TNF-α and splenic IL-1β . The progression of kidney fibrosis was also suppressed in VNS-treated uniIRI mice, compared to the sham stimulation-treated group.

Conclusion

CAP activation after injury could also exert organ protective effect.

Funding

  • Commercial Support