The S1PR1–CCN1 axis drives endothelial-to-mesenchymal transition and vascular instability in brain arteriovenous malformations
Our study identifies the S1PR1-CCN1 axis as a critical regulator of endothelial plasticity in bAVMs. S1PR1 knockdown promotes an EndoMT-like phenotype and enhances endothelial migration, although CCN1 acts as a downstream effector mediating these changes. The in vivo findings in zebrafish further highlight the role of this axis in cerebrovascular instability. Targeting this pathway may offer new therapeutic opportunities to mitigate bAVM progression and rupture risk.
Authors
- Sichen Li (ORCID: https://orcid.org/0000-0001-6045-4395)
- Shiyu Shen (ORCID: https://orcid.org/0000-0001-7287-4223)
- W. J. Zhu (ORCID: https://orcid.org/0000-0003-2618-0436)
- Ganglei Li
- Mingjian Liu (ORCID: https://orcid.org/0000-0002-1055-2138)
- Hongfei Zhang (ORCID: https://orcid.org/0000-0003-2784-8469)
- Yingjun Liu (ORCID: https://orcid.org/0000-0003-1543-1965)
Institutions
- Shanghai Medical College of Fudan University (CN)
- Fudan University (CN)
- Shanghai Public Health Clinical Center (CN)
- National Institute of Neurological Disorders and Stroke (US)
- Shanghai Clinical Research Center (CN)
- Huashan Hospital (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
Publication Details
- Journal
- European journal of medical research
- Published
- 2025-11-25
- DOI
- https://doi.org/10.1186/s40001-025-03484-5
- Primary Topic
- Connective Tissue Growth Factor Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00