Authors
Jiheng Wang, Chenzhu Zhao, Bei Liu, Zhuoyang Wang, Yueru Hou, Yuankun Chen, Wenxing Cui, Kailu Li, Jinyuan Meng, Ge Ren, Tao Xin, Zihao Liu, Xun Wu, Yingxi Wu, Yafei Xue, Gang Zhu, Zhihong Li, Shunnan Ge, Dayun Feng, Yan Qu, Tianzhi Zhao
Published in
Science advances. Volume 12. Issue 27. Pages eaed8653. Jul 03, 2026. Epub Jul 03, 2026.
Abstract
Blood-brain barrier (BBB) disruption is a major pathological feature of traumatic brain injury (TBI) that contributes to secondary damage and poor neurological recovery. Although astrocytes are essential for BBB homeostasis, the molecular basis of astrocyte-associated BBB dysfunction after TBI remains unclear. Here, we found that astrocytic dystrophin protein 71 (Dp71) expression was reduced after TBI in both patients and mouse models. In mice, further experimental down-regulation of astrocytic Dp71 attenuated secondary BBB disruption and was accompanied by reduced astrocyte activation, inflammatory cell infiltration, and matrix metalloproteinase-2 (MMP2) release. Mechanistically, nuclear Dp71 interacted with Wilms tumor 1-associated protein (WTAP) and influenced its ubiquitination, leading to changes in the N6-methyladenosine (m6A) modification, RNA stability, and expression of MMP2 messenger RNA. In addition, biomimetic nanovesicles coated with astrocyte membranes enabled targeted delivery of small interfering RNA targeting Dp71 (siDp71) to astrocytes and reduced MMP2 release and BBB damage after TBI, suggesting a potential therapeutic strategy for mitigating BBB injury after TBI.
PMID:
42397926
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.
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