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Targeting astrocytic Dp71 attenuates BBB disruption after traumatic brain injury through WTAP-associated m<sup>6</sup>A regulation of MMP2.

Overview

Authors: Jiheng Wang1, Chenzhu Zhao1,2, Bei Liu1, Zhuoyang Wang1,2, Yueru Hou1, Yuankun Chen3, Wenxing Cui1, Kailu Li1, Jinyuan Meng1, Ge Ren1, Tao Xin4, Zihao Liu5, Xun Wu1, Yingxi Wu1, Yafei Xue1, Gang Zhu1, Zhihong Li1, Shunnan Ge1, Dayun Feng1, Yan Qu1, Tianzhi Zhao1
ORCID iDs: Jiheng Wang, Chenzhu Zhao, Bei Liu, Yuankun Chen, Wenxing Cui, Tao Xin, Xun Wu, Shunnan Ge, Dayun Feng, Yan Qu, Tianzhi Zhao
  1. Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038 Shaanxi, China
  2. Medical School, Northwest University, Xi’an, 710068 Shaanxi, China
  3. Laboratory of Gene Therapy, Department of Biochemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, 710062 Shaanxi, China
  4. Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China
  5. Department of Neurosurgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan 250021, China
Institutions: Tang Du Hospital (China); Air Force Medical University (China); Northwest University (China); Shaanxi Normal University (China); Shandong First Medical University (China); Shandong Provincial Hospital (China)
Journal: Science advances, volume 12, issue 27, article eaed8653
Dates: received 13 November 2025; accepted 18 May 2026; published online 3 July 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1126/sciadv.aed8653 · PMID 42397926 · PMCID PMC13330862 · OpenAlex W7167224754
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), traumatic brain injury (population), cellular / molecular (subfield)
Methods: Statistics
MeSH: Adenosine*, Astrocytes*, Blood-Brain Barrier*, Brain Injuries, Traumatic*, Matrix Metalloproteinase 2*, Animals, Disease Models, Animal, Humans, Male, Mice, RNA Methylation, RNA, Small Interfering (* major topic)
Journal subjects: Neuroscience, Cellular Neuroscience
Topic: RNA modifications and cancer (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Natural Science Foundation of China (81971153, 81200902, 82130038)
Citations: not cited yet (Europe PMC); 49 references in the paper

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 21 authors, 12 MeSH terms, 1 funder, 49 references.

Cite

This paper

Wang, J., Zhao, C., Liu, B., Wang, Z., Hou, Y., Chen, Y., Cui, W., Li, K., Meng, J., Ren, G., Xin, T., Liu, Z., Wu, X., Wu, Y., Xue, Y., Zhu, G., Li, Z., Ge, S., Feng, D., . . . Zhao, T. (2026). Targeting astrocytic Dp71 attenuates BBB disruption after traumatic brain injury through WTAP-associated m<sup>6</sup>A regulation of MMP2. Science advances, 12(27), eaed8653. https://doi.org/10.1126/sciadv.aed8653

BibTeX

@article{wang2026targeting,
author = {Wang, Jiheng and Zhao, Chenzhu and Liu, Bei and Wang, Zhuoyang and Hou, Yueru and Chen, Yuankun and Cui, Wenxing and Li, Kailu and Meng, Jinyuan and Ren, Ge and Xin, Tao and Liu, Zihao and Wu, Xun and Wu, Yingxi and Xue, Yafei and Zhu, Gang and Li, Zhihong and Ge, Shunnan and Feng, Dayun and Qu, Yan and Zhao, Tianzhi},
title = {{Targeting astrocytic Dp71 attenuates BBB disruption after traumatic brain injury through WTAP-associated m\<sup\>6\</sup\>A regulation of MMP2}},
journal = {Science advances},
year = {2026},
month = jul,
volume = {12},
number = {27},
pages = {eaed8653},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.aed8653},
url = {https://doi.org/10.1126/sciadv.aed8653},
pmid = {42397926},
pmcid = {PMC13330862}
}

RIS

TY - JOUR
AU - Wang, Jiheng
AU - Zhao, Chenzhu
AU - Liu, Bei
AU - Wang, Zhuoyang
AU - Hou, Yueru
AU - Chen, Yuankun
AU - Cui, Wenxing
AU - Li, Kailu
AU - Meng, Jinyuan
AU - Ren, Ge
AU - Xin, Tao
AU - Liu, Zihao
AU - Wu, Xun
AU - Wu, Yingxi
AU - Xue, Yafei
AU - Zhu, Gang
AU - Li, Zhihong
AU - Ge, Shunnan
AU - Feng, Dayun
AU - Qu, Yan
AU - Zhao, Tianzhi
TI - Targeting astrocytic Dp71 attenuates BBB disruption after traumatic brain injury through WTAP-associated m<sup>6</sup>A regulation of MMP2
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/07/03
VL - 12
IS - 27
SP - eaed8653
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.aed8653
UR - https://doi.org/10.1126/sciadv.aed8653
LA - en
ER -

CSL-JSON

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