ArticleDiagnostics (Basel, Switzerland)2024
Whole-Genome Omics Elucidates the Role of CCM1 and Progesterone in Cerebral Cavernous Malformations within CmPn Networks.
Article in Diagnostics (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Single-cell transcriptome profiling reveals dynamic cell populations and immune infiltration in cerebral cavernous malformation.Frontiers in immunology · 2025Article
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7 authors.
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Abstract
Cerebral cavernous malformations (CCMs) are abnormal expansions of brain capillaries that increase the risk of hemorrhagic strokes, with CCM1 mutations responsible for about 50% of familial cases. The disorder can cause irreversible brain damage by compromising the blood-brain barrier (BBB), leading to fatal brain hemorrhages. Studies show that progesterone and its derivatives significantly impact BBB integrity. The three CCM proteins (CCM1, CCM2, and CCM3) form the CCM signaling complex (CSC), linking classic and non-classic progesterone signaling within the CmPn network, which is crucial for maintaining BBB integrity. This study aimed to explore the relationship between CCM1 and key pathways of the CmPn signaling network using three mouse embryonic fibroblast lines (MEFs) with distinct CCM1 expressions. Omics and systems biology analysis investigated CCM1-mediated signaling within the CmPn network. Our findings reveal that CCM1 is essential for regulating cellular processes within progesterone-mediated CmPn/CmP signaling, playing a crucial role in maintaining microvessel integrity. This regulation occurs partly through gene transcription control. The critical role of CCM1 in these processes suggests it could be a promising therapeutic target for CCMs.
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