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July 10, 2026Communications BiologyOpen Access

Notch signaling pathway mediates anti-inflammatory effects of vagus nerve stimulation during lipopolysaccharide-induced acute kidney injury

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Authors

SKShuhei KuwabaraHIHiro InoueWNWilliam Nash

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Overview

Randomized trial finds Notch signaling mediates anti-inflammatory effects in a mouse model of acute kidney injury, indicating therapeutic potential for sepsis.

Key Points

  • This research aims to explore the role of the Notch signaling pathway in mediating the anti-inflammatory effects of vagus nerve stimulation during acute kidney injury induced by lipopolysaccharide.
  • Utilized a mouse model of LPS-induced acute kidney injury for investigation.
  • Assessed Notch2 signaling effects in macrophages following activation of the cholinergic anti-inflammatory pathway via vagus nerve stimulation.
  • Evaluated the impact of macrophage-specific Notch2 knockout on the anti-inflammatory effects of vagus nerve stimulation.
  • Vagus nerve stimulation enhanced Notch2 signaling in macrophages, reducing inflammation in the spleen and kidney damage.
  • Macrophage-specific knockout of Notch2 diminished the anti-inflammatory effects of vagus nerve stimulation.
  • Vagus nerve stimulation and Notch2 signaling were associated with increased transferrin levels, aiding in iron homeostasis and kidney protection.

Cite This Study

Kuwabara et al. (2026) studied this question.

synapsesocial.com/papers/6a508afd6eeac72a4379ff88https://doi.org/10.1038/s42003-026-10620-2
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1α7 nicotinic acetylcholine receptor agonist attenuates lipopolysaccharide-induced acute kidney injury in mice by reducing CCL2 expression in macrophages2025
  2. 2Inhibition of Notch signaling pathway attenuates sympathetic hyperinnervation together with the augmentation of M2 macrophages in rats post-myocardial infarction2015 · 75 citations
  3. 3Notch1 Inhibition Exacerbates APAP-Induced Liver Injury via β-Catenin and Macrophage Polarization2025
  4. 4Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes2016 · 321 citations
  5. 5Norepinephrine ameliorates sepsis-associated acute kidney injury through inhibiting damage of renal tubular epithelium induced by macrophage inflammatory response2025