{
  "abstract": "Objective To explore the effects of Complement Component 5a (C5a) on central nervous system vasculitis and its molecular mechanism. Methods Bioinformatics analysis was conducted using the GSE68004 dataset (comprising 76 cases of vasculitis and 37 control samples).Endothelial cells were subjected to different treatments, and protein expression was determined by Western blot. Fibroblasts were cultured after different stimulations. Immunofluorescence was employed to detect the fluorescence intensity of α-SMA, and the CCK-8 assay was used to detect cell proliferation. Results Bioinformatics analysis reveals a significant positive correlation between C5a and the activation of the PI3K/ERK/AKT pathway (p < 0.05). In vitro experiments shows that stimulation with C5a (10 nM) significantly increases the protein expression of P-PI3K, P-ERK1/2, HIF1α and ROBO4 in endothelial cells (p < 0.05), while significantly reducing the expression of tight junction proteins (ZO-1, occludin, claudin-5) (p < 0.05). In fibroblasts, C5a stimulation increases the protein expression of P-CREB, fibronectin and α-SMA (p < 0.05), and promotes TGF-β1 secretion (p < 0.05). The use of PI3K/ERK inhibitor D-87503 or specific siRNA knockdown of ERK/CREB can significantly reverse these effects. Conclusion In vitro, Complement C5a may disrupt the endothelial barrier function and promote fibrosis and proliferation of fibroblasts, potentially through activating the PI3K/ERK/HIF1α/ROBO4 pathway in endothelial cells or the CREB pathway in fibroblasts. These processes are recognized as key pathological features of central nervous system vasculitis, suggesting that C5a may contribute to their progression.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatric, The Second Hospital of Hebei Medical University",
    "Hebei Key Laboratory of Vascular Homeostasis, Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease",
    "Department of Pediatric, The First Rongjun Special Care Hospital of Hebei Province"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xinyi Men"
    },
    {
      "affs": [
        1
      ],
      "name": "Hui Ji"
    },
    {
      "affs": [
        2
      ],
      "name": "Jing Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Yongchun Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiuxia Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyu Tian"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiangjian Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3vyegpc3p5fdr.bib",
  "cited_by": 0,
  "doi": "10.1186/s40001-026-04957-x",
  "fulltext_url": "https://doi.org/10.1186/s40001-026-04957-x",
  "id": "3vyegpc3p5fdr",
  "issns": [
    "2047-783X"
  ],
  "landing_url": "https://doi.org/10.1186/s40001-026-04957-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2403|Complement system in diseases"
    ]
  ],
  "openalex": "W7170168282",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/3vyegpc3p5fdr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:46Z",
      "native_id": "9090534458e142eabd9492b1dee61adc",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s40001-026-04957-x"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Complement system in diseases",
      "subfield": "immunology"
    }
  ],
  "title": "C5a drives central nervous system vasculitis in endothelial cells and fibroblasts via modulating the PI3K/ERK/CREB signaling pathways",
  "title_text": "C5a drives central nervous system vasculitis in endothelial cells and fibroblasts via modulating the PI3K/ERK/CREB signaling pathways",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:46Z",
  "url": "https://research.draconitic.com/paper/3vyegpc3p5fdr",
  "venue": "European Journal of Medical Research",
  "versions": []
}