{
  "abstract": "Endothelial dysfunction contributes to multi-organ injury in sepsis, but the underlying mechanisms remain incompletely understood. Here we show that endothelial ubiquitin-specific protease 28 (USP28) is increased in patients with sepsis and in male mice in a murine polymicrobial sepsis model. Mechanistically, USP28 stabilizes non-muscle myosin heavy chain IIA (NMMHC IIA) by removing K48-linked ubiquitination at K1413. Moreover, NMMHC IIA promotes interferon-α/β receptor 1 (IFNAR1) trafficking to the plasma membrane, enhancing IFNAR1/signal transducer and activator of transcription 1 (STAT1) signaling and endothelial necroptosis. In turn, STAT1 transcriptionally increases USP28 expression, forming a positive feedback loop. Endothelial USP28 deletion or pharmacological inhibition attenuates sepsis-induced multi-organ injury, whereas USP28 overexpression exacerbates it. Conversely, endothelial NMMHC IIA or IFNAR1 overexpression largely abrogates the protection conferred by USP28 deficiency in septic male mice. These findings identify a USP28–NMMHC IIA axis that promotes endothelial necroptosis and multi-organ injury in sepsis through IFNAR1/STAT1 signaling.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Jiahui Tang"
    },
    {
      "name": "Dingji Hu"
    },
    {
      "name": "Mengchen Xu"
    },
    {
      "name": "Haiyu Chen"
    },
    {
      "name": "Shuaishuai Gong"
    },
    {
      "name": "Fang Li",
      "orcid": "0000-0002-7617-6534"
    },
    {
      "name": "Boyang Yu"
    },
    {
      "name": "Yuanyuan Zhang",
      "orcid": "0000-0002-3662-4398"
    },
    {
      "name": "Songqiao Liu",
      "orcid": "0000-0002-1875-1131"
    },
    {
      "name": "Junping Kou",
      "orcid": "0000-0001-8377-915X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3ykbdq465fabk.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78666-8",
  "fulltext_url": null,
  "id": "3ykbdq465fabk",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78666-8",
  "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": [
    [
      "openalex",
      "2713|Sepsis Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7222682881",
  "pdf_url": "https://www.nature.com/articles/s41467-026-78666-8_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/3ykbdq465fabk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-78666-8",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78666-8"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Sepsis Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "USP28 potentiates endothelial necroptosis via deubiquitinating NMMHC IIA in septic male mice",
  "title_text": "USP28 potentiates endothelial necroptosis via deubiquitinating NMMHC IIA in septic male mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:38Z",
  "url": "https://research.draconitic.com/paper/3ykbdq465fabk",
  "venue": "Nature Communications",
  "versions": []
}