RBM3 enhances the stability of MEF2C mRNA and modulates blood-brain barrier permeability in AD microenvironment

Abstract

Blood-brain barrier (BBB) changes are acknowledged as early indicators of Alzheimer's disease (AD). The permeability and integrity of the BBB rely significantly on the essential role played by the tight junction proteins (TJPs) connecting endothelial cells. This study found the reduced RNA binding motif protein 3 (RBM3) expression in brain microvascular endothelial cells (BMECs) incubated with Aβ1–42. This downregulation of RBM3 caused a decrease in the levels of ZO-1 and occludin and increased the permeability of BBB cell model in AD microenvironment. Myocyte enhancer factor 2C (MEF2C) expression was also inhibited in BMECs incubated with Aβ1–42. A decrease in MEF2C expression led to increased permeability of BBB cell model in AD microenvironment and reductions in the levels of ZO-1 and occludin. Further analysis of the underlying mechanism revealed that RBM3 binds to and stabilizes MEF2C mRNA. MEF2C binds to the promoters of ZO-1 and occludin, enhancing their transcriptional activities and modulating BBB permeability. RBM3 increases the stability of MEF2C mRNA and subsequently modulates BBB permeability through the paracellular pathway of TJPs. This may provide new insights for AD research.