Serum exosome miR-208b-3p worsens cerebral microvascular endothelial cell injury by inhibiting NLK expression

BACKGROUND: Traumatic brain injury (TBI) can cause pathological disruption of the blood-brain barrier, leading to neurological damage. Recent studies suggest that microRNA-208b-3p (miR-208b-3p) in serum exosomes may play a role in TBI, but its precise mechanism remains unclear. This study aims to investigate the effect of serum exosomal miR-208b-3p on brain microvascular endothelial cells (BMVECs) and its regulatory mechanism involving Nemo-like kinase (NLK).METHODS: Serum exosomes were extracted from patients with TBI and co-cultured with BMVECs following scratch injury. The expression levels of tight junction proteins, inflammatory factors, and NLK in BMVECs were measured using Western blotting and quantitative real-time PCR (QRT-PCR). The levels of miR-208b-3p in exosomes were also assessed. Bioinformatics analysis and a dual luciferase assay were used to confirm the targeting relationship between miR-208b-3p and NLK.RESULTS: Serum exosomes from TBI patients were found to be rich in miR-208b-3p. miR-208b-3p was shown to regulate apoptosis in BMVECs and directly target NLK, leading to its reduced expression following scratch injury. Downregulation of NLK was associated with increased endothelial cell damage and impaired nerve repair.CONCLUSIONS: Serum exosomal miR-208b-3p exacerbates traumatic injury by downregulating NLK expression in BMVECs, thereby aggravating blood-brain barrier disruption and impeding neural repair. These findings provide a potential therapeutic target for the treatment of traumatic brain injuries.