{
  "abstract": "Cerebral cavernous malformations (CCMs) cause hemorrhagic stroke and lack effective pharmacological therapies. Although multiple extracellular stimuli contribute to CCM progression, how these signals are integrated across the plasma membrane remains unclear. Through transcriptomic analysis, we identified dipeptidyl peptidase-4 (DPP4) as a hub gene that may link extracellular stimuli to endothelial dysfunction, with elevated expression in CCM lesions. DPP4 is a type Ⅱ transmembrane glycoprotein that possesses both enzymatic and non-enzymatic functions. DPP4 knockdown reverses endothelial dysfunction in vitro and suppresses CCM progression in vivo. Single-cell transcriptomic analysis further reveals that DPP4 promotes pro-angiogenic signaling and is associated with caveolin-1 (CAV1). Mechanistically, our data suggest that DPP4 promotes CCM pathogenesis via a non-enzymatic interaction with CAV1, largely independent of its canonical enzymatic activity. This interaction promotes CAV1 phosphorylation and downstream FAK signaling activation. To selectively target the predicted interface epitope on DPP4, we developed a structure-guided nanobody (DC499-mFc) and functionally disrupted the DPP4-CAV1 interaction. This nanobody-based strategy effectively attenuates CCM progression in vivo. Collectively, these findings suggest that DPP4 contributes to CCM progression and point to nanobody‑based disruption of the non‑enzymatic DPP4-CAV1 interaction as a potential therapeutic strategy for CCM.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang province, China.",
    "NHC Key Laboratory of Cell Transplantation, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.",
    "Department of Critical Care Medicine, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.",
    "First Affiliated Hospital of Ningbo University, Zhejiang, China.",
    "Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang province, China. changbinshi@hotmail.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Chunyang Men"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ziyu Xiong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qianpeng Duan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jiaxin Cheng"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiqing Luo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bao Yang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ying Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Cong Yan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuwen Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yongqing Ye"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rui Bi"
    },
    {
      "affs": [
        3
      ],
      "name": "Zifeng Dai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Silengtu Hu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xia Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenzhong Du"
    },
    {
      "affs": [
        0
      ],
      "name": "Dongdong Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Changbin Shi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6bzfnshqyfns4.bib",
  "cited_by": 0,
  "doi": "10.1186/s12951-026-04898-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13726199",
  "id": "6bzfnshqyfns4",
  "issns": [
    "1477-3155"
  ],
  "landing_url": "https://europepmc.org/article/MED/42968142",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2728|Vascular Malformations Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7172499193",
  "pdf_url": "https://europepmc.org/articles/PMC13726199?pdf=render",
  "pmcid": "PMC13726199",
  "pmid": "42968142",
  "published": "2026-08-05",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/6bzfnshqyfns4.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42968142",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42968142"
    },
    {
      "first_seen": "2026-11-05T12:22:35Z",
      "native_id": "PMC13726199",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12951-026-04898-x"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Vascular Malformations Diagnosis and Treatment",
      "subfield": "neurology"
    }
  ],
  "title": "Targeting the non-enzymatic function of DPP4 via a nanobody inhibits cerebral cavernous malformation progression.",
  "title_text": "Targeting the non-enzymatic function of DPP4 via a nanobody inhibits cerebral cavernous malformation progression.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:13Z",
  "url": "https://research.draconitic.com/paper/6bzfnshqyfns4",
  "venue": "Journal of nanobiotechnology",
  "versions": []
}