{
  "abstract": "IntroductionIntervertebral disc degeneration (IVDD) is a primary cause of low back pain, but its molecular mechanisms remain poorly understood, limiting therapeutic development. This study investigates the role of aquaporin 9 (AQP9) in IVDD and its regulation of macrophage M1 polarization through the NF-κB pathway.MethodsAQP9 expression was examined in degenerated nucleus pulposus (NP) tissues from both rodent models and human clinical samples. The functional role of AQP9 was assessed using AAV-mediated AQP9 overexpression and pharmacological inhibition of AQP9. The involvement of the NF-κB pathway was evaluated using an NF-κB specific inhibitor, with M1/M2 macrophage polarization analyzed in vivo and in vitro.ResultsAQP9 expression was significantly upregulated in degenerated NP tissues from both rodent models and human clinical samples. Functionally, AAV-mediated AQP9 overexpression exacerbated IVDD and extracellular matrix (ECM) degradation, while pharmacological inhibition of AQP9 exerted protective effects. Mechanistically, AQP9 directly bound to p65, inhibiting its ubiquitin-proteasome degradation and thereby prolonging p65 protein half-life and enhancing its stability. This sustained p65 activation continuously stimulated the NF-κB pathway, driving macrophage polarization toward a pro-inflammatory M1 phenotype, as evidenced by increased M1 markers and an elevated M1/M2 ratio in vivo and in vitro. The pro-inflammatory and catabolic effects of AQP9 were completely abrogated by an NF-κB specific inhibitor, confirming pathway dependence.DiscussionOur findings elucidate a non-canonical function of AQP9 as a p65 stabilizer, establishing a novel “AQP9-p65-macrophage plasticity” axis that drives IVDD. This work positions AQP9 as a promising diagnostic biomarker and therapeutic target for IVDD, and suggests its potential relevance in other inflammatory degenerative diseases.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Kewu Tu"
    },
    {
      "name": "Tao Zhu"
    },
    {
      "name": "Jinming Xu"
    },
    {
      "name": "Kun Zhao"
    },
    {
      "name": "Dongteng Liao"
    },
    {
      "name": "Zhaomou Chen"
    },
    {
      "name": "Yunhua Luo"
    },
    {
      "name": "Weijie Lai"
    },
    {
      "name": "Jinrong Liang"
    },
    {
      "name": "Chaolong Lu"
    },
    {
      "name": "Ying Yang"
    },
    {
      "name": "Zhengbo Hu"
    },
    {
      "name": "Qiang Wu"
    },
    {
      "name": "Xiangheng Dai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0f232f7gqgfsr.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1954935",
  "fulltext_url": null,
  "id": "0f232f7gqgfsr",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1954935",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0f232f7gqgfsr.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T06:20:21Z",
      "native_id": "10.3389/fimmu.2026.1954935",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1954935"
    },
    {
      "first_seen": "2026-11-02T12:23:23Z",
      "native_id": "10.3389/fimmu.2026.1954935",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1954935/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Aquaporin 9 drives macrophage M1 polarization and intervertebral disc degeneration by stabilizing p65 to activate NF-κB signaling",
  "title_text": "Aquaporin 9 drives macrophage M1 polarization and intervertebral disc degeneration by stabilizing p65 to activate NF-κB signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T00:25:32Z",
  "url": "https://research.draconitic.com/paper/0f232f7gqgfsr",
  "venue": "Frontiers in Immunology",
  "versions": []
}