miR-21a-5p targets DDX58 to suppress TLR2/NF-κB signaling and protect the blood-brain barrier after injury.

Authors

Jing Yang, Ning Tang, Ruanxian Dai, Hao Fu, Shiyi Li, Qiang Meng

Published in

Molecular biology reports. Volume 53. Issue 1. Oct 25, 2026. Epub Oct 25, 2026.

Abstract

Damage to the blood-brain barrier (BBB) plays a pivotal role in the pathogenesis of various neurological disorders. miR-21a-5p has been implicated in the modulation of BBB injury. Understanding the molecular targets of miR-21a-5p is crucial for developing targeted interventions in BBB repair.
The target gene of miR-21a-5p was identified through bioinformatics analysis and validated using a dual luciferase reporter assay. The expression of target gene was further confirmed in both in vivo and in vitro models of BBB injury. BBB injury cell models were employed to assess the effects of target gene overexpression and silencing on brain microvascular endothelial cell (BMEC) activity, as well as on the TLR2/NF-κB signaling pathway and associated BBB proteins. miR-21a-5p overexpression and silencing were utilized to assess the impact of target gene on BBB integrity.
DDX58 was identified as a direct target of miR-21a-5p and is shown to modulate BBB injury. DDX58 expression was found to be upregulated in models of BBB damage. Exosomes containing miR-21a-5p mitigated BBB damage, which was associated with downregulated DDX58 expression in vivo and in vitro. Overexpression of DDX58 in BMECs resulted in reduced cellular viability, increased expression of TLR2 and phosphorylated p65 (p-p65), as well as elevated levels of matrix metalloproteinases (MMP-2/9), which are associated with BBB disruption. This was accompanied by a reduction in tight junction proteins, including claudin-5, occludin, and ZO-1. Conversely, silencing DDX58 expression exhibited the opposite effects. Both miR-21a-5p treatment and DDX58 interference alleviated BBB injury. Co-overexpression of DDX58 during miR-21a-5p treatment reversed the protective effects of miR-21a-5p, exacerbating BBB injury.
miR-21a-5p targets and downregulates DDX58, which is associated with reduced expression of TLR2/NF-κB-related markers, decreased MMP-2/9 levels, and protection of tight junction integrity.

PMID:
42927575
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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