Abstract
Brain endothelial cells (ECs) are essential elements of the blood-brain barrier (BBB), maintaining its integrity through both paracellular junctions and transcellular transport systems. Myosin IIA, a multifunctional protein, plays a significant role in various cellular processes, including cytoskeletal maintenance, cell division, and signal transduction. While Myosin IIA has been implicated in bleeding and ischemic stroke, its role in regulating BBB integrity under physiological conditions remains unclear. In this study, we investigated the impact of Myosin IIA deficiency on BBB integrity using intravenous tracer injections and models of epilepsy. Flow cytometry, Western blot, and real-time PCR were employed to isolate brain cells and assess changes in protein and mRNA levels. Additionally, immunofluorescence staining and electron microscopy were used to explore alterations in protein expression and the structure of BBB. Our results demonstrate that endothelial Myosin IIA deficiency increased BBB permeability and exacerbated symptoms in BBB-related diseases. Mechanistically, we found that Myosin IIA modulates β-catenin transcription and protein interactions. The overexpression of β-catenin in brain endothelial Myosin IIA deficiency mice improved BBB integrity and reduced disease severity. This study establishes Myosin IIA as a critical regulator of BBB integrity and suggests new therapeutic targets for vascular diseases.