{
  "abstract": "The cholinergic anti-inflammatory pathway (CAP) plays a central role in neuroimmunomodulation, and its activation is a potential strategy for ameliorating sepsis-associated acute kidney injury (SA-AKI). However, further investigations are necessary to understand the molecular mechanisms of CAP activation and develop therapies for SA-AKI. Here, we tested whether the Notch signaling pathway, which regulates cell-cell interactions, mediates the anti-inflammatory effects of CAP. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we found that CAP activation by vagus nerve stimulation (VNS) enhanced Notch2 signaling in macrophages, mitigating inflammation in the spleen and tissue damage in the kidneys. Consistently, macrophage-specific knockout of Notch2 resulted in an attenuation of these anti-inflammatory effects of VNS. We also demonstrated that VNS and macrophage-specific Notch2 signaling might upregulate transferrin, which maintains iron homeostasis, thereby protecting the kidneys. Taken together, our findings suggest the involvement of Notch signaling in the mechanisms of VNS-mediated CAP activation during LPS-induced AKI.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, VA USA",
    "Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba, Japan",
    "Research Institute of Disaster Medicine (RIDM), Chiba University, Chiba, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Shuhei Kuwabara",
      "orcid": "0000-0002-4324-2582"
    },
    {
      "affs": [
        0
      ],
      "name": "Hiro Inoue"
    },
    {
      "affs": [
        0
      ],
      "name": "William T. Nash"
    },
    {
      "affs": [
        0
      ],
      "name": "Junlan Yao",
      "orcid": "0009-0004-2411-742X"
    },
    {
      "affs": [
        0
      ],
      "name": "Vikram Sabapathy",
      "orcid": "0000-0002-7319-0998"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuqiu Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Rahul Sharma"
    },
    {
      "affs": [
        1
      ],
      "name": "Ryo Hatano"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Takashi Miki",
      "orcid": "0000-0001-5741-1626"
    },
    {
      "affs": [
        0
      ],
      "name": "Mark D. Okusa",
      "orcid": "0000-0002-0801-0532"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3g4hq3kq5rb9d.bib",
  "cited_by": 0,
  "doi": "10.1038/s42003-026-10620-2",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13720128/",
  "id": "3g4hq3kq5rb9d",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://doi.org/10.1038/s42003-026-10620-2",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2808|Vagus Nerve Stimulation Research"
    ]
  ],
  "openalex": "W7167579333",
  "pdf_url": "https://www.nature.com/articles/s42003-026-10620-2_reference.pdf",
  "pmcid": "PMC13720128",
  "pmid": "42414583",
  "published": "2026-07-07",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/3g4hq3kq5rb9d.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:23:58Z",
      "native_id": "PMC13720128",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s42003-026-10620-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Vagus Nerve Stimulation Research",
      "subfield": "neurology"
    }
  ],
  "title": "Notch signaling pathway mediates anti-inflammatory effects of vagus nerve stimulation during lipopolysaccharide-induced acute kidney injury",
  "title_text": "Notch signaling pathway mediates anti-inflammatory effects of vagus nerve stimulation during lipopolysaccharide-induced acute kidney injury",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:04Z",
  "url": "https://research.draconitic.com/paper/3g4hq3kq5rb9d",
  "venue": "Communications Biology",
  "versions": []
}