{
  "abstract": "A high-fat diet (HFD) induces low-grade intestinal inflammation, thereby causing structural and functional impairments of the enteric nervous system (ENS). Nucleotide oligomerization domain (NOD)-like receptor (NLR) containing a caspase activation and recruitment domain 3 (NLRC3) participates in key pathophysiological processes related to inflammation, immunity, and proliferative diseases. However, the function of NLRC3 within the ENS remains to be clarified. This investigation was designed to characterize NLRC3 expression and distribution within the ENS and to elucidate its mechanism in modulating ENS injury. An HFD-induced low-grade colonic inflammation model was established in NLRC3 gene knockout (Nlrc3−/−) mice and wild-type (WT) C57BL/6J mice. The influence of NLRC3 on ENS architecture and motor function was assessed using morphological evaluation, molecular biological assays, and colonic motility analyses. The findings demonstrated that NLRC3 was primarily distributed within the cytoplasm of ENS neurons in mice, with HFD decreasing NLRC3 expression in enteric neurons. Relative to WT mice, HFD-treated Nlrc3−/− mice developed more pronounced ENS injury, characterized by enteric glial cells proliferation and activation, enteric neuronal loss accompanied by structural disruption, and a further delay in colonic transit function. NLRC3 deficiency exacerbated HFD-induced ENS injury and enteric neuronal apoptosis via nuclear factor-κB signaling pathway activation. These observations establish NLRC3 as a key negative regulator of neuroinflammatory responses in the ENS. As a negative regulatory pattern recognition receptor that links innate immunity with ENS signaling, NLRC3 may represent a promising therapeutic target.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00018-026-06364-1.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Human Anatomy, Basic Medical College, Guangxi Medical University, Nanning, 530000 China",
    "Department of Anatomy and K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi’an, 710032 China",
    "College of Life Science, Northwest University, Xi’an, 710069 China",
    "Department of Endocrinology, Xijing Hospital, The Fourth Medical University, Xi’an, 710038 China",
    "Department of Human Anatomy, Basic Medical College, Zunyi Medical University, Zunyi, 563006 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yan Wang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yan Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Meng-Ying Li"
    },
    {
      "affs": [
        4
      ],
      "name": "Sha-Sha Tao"
    },
    {
      "affs": [
        0
      ],
      "name": "Guo-He Tan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yun-Qing Li",
      "orcid": "0000-0002-3707-3348"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2xmrbrvtj8p0h.bib",
  "cited_by": 0,
  "doi": "10.1007/s00018-026-06364-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710505/",
  "id": "2xmrbrvtj8p0h",
  "issns": [
    "1420-682X",
    "1420-9071"
  ],
  "landing_url": "https://doi.org/10.1007/s00018-026-06364-1",
  "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",
      "Original Article"
    ],
    [
      "openalex",
      "2715|Gastrointestinal motility and disorders"
    ]
  ],
  "openalex": "W7171464259",
  "pdf_url": null,
  "pmcid": "PMC13710505",
  "pmid": "42934422",
  "published": "2026-07-27",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/2xmrbrvtj8p0h.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:28Z",
      "native_id": "PMC13710505",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00018-026-06364-1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2715|Gastrointestinal motility and disorders",
      "subfield": "general"
    }
  ],
  "title": "NLRC3 deficiency exacerbates high-fat diet-induced enteric nervous system injury and colonic motility dysfunction in mice via activating NF-κB signaling pathway",
  "title_text": "NLRC3 deficiency exacerbates high-fat diet-induced enteric nervous system injury and colonic motility dysfunction in mice via activating NF-κB signaling pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:28Z",
  "url": "https://research.draconitic.com/paper/2xmrbrvtj8p0h",
  "venue": "Cellular and Molecular Life Sciences: CMLS",
  "versions": []
}