TIE2 links MEKK3-KLF2/4 and PI3K signaling in cerebral cavernous malformation - PubMed
4 hours ago
- #Endothelial Cells
- #Cerebral Cavernous Malformation
- #TIE2 Signaling
- Cerebral cavernous malformations (CCMs) are vascular lesions that can cause strokes and seizures, with growth driven by endothelial cell signaling pathways.
- Enhanced MEKK3-KLF2/4 signaling stimulates PI3K signaling in CCMs, but the connection between these pathways was previously unknown.
- Using human CCM specimens, mouse models, and human endothelial cells, the study found no significant role for VEGFR2 in CCM formation.
- Increased phospho-TIE2 levels were observed in human and mouse CCM lesions, with MEKK3-KLF2/4 driving TIE2 receptor expression.
- Genetic or pharmacologic blockade of TIE2 almost completely rescued CCM formation in mouse models, identifying TIE2 as the link between MEKK3-KLF2/4 and PI3K signaling.
- Targeting TIE2 may be an effective therapeutic strategy for treating human CCM disease.