OSCR

Endothelial miR-15a/16-1 Regulation of SYNE1 Mediates Structural and Functional Recovery after Traumatic Brain Injury.

Overview

Authors: Shun Li1,2, Na Qiu1,2, Chao Zhou1, Andrew Ni1,3, Ping Sun1,2, Jia‐Jun Liu4,5,6, Xin‐Lei Huang1, Tian‐Qing Xiong1, Yu‐Chi Zhang1,2, Hai‐Zhou Liu1,2, Xiao‐Tao Xu1, Rui Wang1, Shi‐Qing Zhang1, Yu‐Xin Zhang1, Silvia Liu4,5,6, C Edward Dixon2,7, Jun Chen1,2, Ke‐Jie Yin1,2
ORCID iDs: Shun Li, Na Qiu, Andrew Ni, Ping Sun, Jia‐Jun Liu, Yu‐Chi Zhang, Hai‐Zhou Liu, Xiao‐Tao Xu, Shi‐Qing Zhang, Yu‐Xin Zhang, Silvia Liu, Jun Chen, Ke‐Jie Yin
  1. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  2. Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
  3. Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA
  4. Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  5. Organ Pathobiology and Therapeutics Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  6. Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  7. Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Institutions: University of Pittsburgh (United States); Geriatric Research Education and Clinical Center (United States); VA Pittsburgh Healthcare System (United States); Brown University (United States)
Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany), article e77111
Dates: received 25 March 2026; accepted 3 August 2026; published online 12 August 2026; in print August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/advs.77111 · PMID 42584458 · PMCID PMC13464459 · OpenAlex W7202255850
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: traumatic brain injury (population), cellular / molecular (subfield)
Methods: Preprocessing, Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, Machine learning, Evoked potentials, Connectivity, fMRI & imaging
Keywords: endothelial signaling, miR‐15a/16‐1, neurovascular recovery, SYNE1, TBI, white and gray matter integrity
Topic: Barrier Structure and Function Studies (Neurology, Neuroscience), according to OpenAlex
Funding: Department of Veterans Affairs Merit Review grants (I01BX003377, I01BX004837, I01BX005750); BLRD VA (I01 BX005750, I01 BX003377, I01 BX004837); Department of Veterans Affairs Senior Research Career Scientist Award (821-RC-NB-30556); NIH HHS (S10 OD028483, S10OD028483); NIH/NIGMS (R35GM159862); NIGMS NIH HHS (R35 GM159862)
Citations: not cited yet (Europe PMC); 64 references in the paper

Abstract

Traumatic brain injury (TBI) disrupts the blood–brain barrier (BBB) and compromises endothelial function, leading to persistent neurological dysfunction. Although miR‐15a/16‐1 deletion has recently been shown to be neuroprotective in brain injury, the endothelial pathways mediating long‐term structural and functional recovery after TBI remain unknown. Here, we demonstrate endothelial cell‐specific deletion of miR‐15a/16‐1 is sufficient to confer neurorestoration after TBI by reducing acute BBB leakage, preserving white and gray matter integrity, and accelerating sensorimotor and cognitive recovery. Mechanistically, transcriptomic profiling identified SYNE1 as a direct downstream target of miR‐15a/16‐1, validated via in‐silico binding prediction and 3’‐UTR luciferase assays. Crucially, endothelial cell‐targeted AAV‐mediated knockdown of SYNE1 abrogated the neurorestorative effects of miR‐15a/16‐1 deletion, indicating SYNE1 is required for its function. Furthermore, single‐cell RNA‐seq analysis of human TBI tissue demonstrates significant downregulation of SYNE1 in endothelial cells within the contusion core relative to pericontusional endothelium. Together, these findings define a previously unrecognized miR‐15a/16‐1–SYNE1 axis that promotes endothelial repair after TBI, with significant translational potential.

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

Code

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Data

Datasets cited

Data Availability Statement

The data that support the findings of this study are available within the article and its Supporting Information. The mouse bulk RNA‐seq data have been deposited in the GEO database with accession ID GSE319914 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319914). The human scRNA‐seq data used in this study for second‐hand data mining were downloaded from the public GEO database with accession ID GSE182398 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE182398). Additional data are available from the corresponding author upon reasonable request.

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

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, pages, dates, 18 authors, 6 keywords, 6 funders, 64 references.

Cite

This paper

Li, S., Qiu, N., Zhou, C., Ni, A., Sun, P., Liu, J., Huang, X., Xiong, T., Zhang, Y., Liu, H., Xu, X., Wang, R., Zhang, S., Zhang, Y., Liu, S., Dixon, C. E., Chen, J., & Yin, K. (2026). Endothelial miR-15a/16-1 Regulation of SYNE1 Mediates Structural and Functional Recovery after Traumatic Brain Injury. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e77111. https://doi.org/10.1002/advs.77111

BibTeX

@article{li2026endothelial,
author = {Li, Shun and Qiu, Na and Zhou, Chao and Ni, Andrew and Sun, Ping and Liu, Jia‐Jun and Huang, Xin‐Lei and Xiong, Tian‐Qing and Zhang, Yu‐Chi and Liu, Hai‐Zhou and Xu, Xiao‐Tao and Wang, Rui and Zhang, Shi‐Qing and Zhang, Yu‐Xin and Liu, Silvia and Dixon, C Edward and Chen, Jun and Yin, Ke‐Jie},
title = {{Endothelial miR-15a/16-1 Regulation of SYNE1 Mediates Structural and Functional Recovery after Traumatic Brain Injury}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = aug,
pages = {e77111},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/advs.77111},
url = {https://doi.org/10.1002/advs.77111},
pmid = {42584458},
pmcid = {PMC13464459}
}

RIS

TY - JOUR
AU - Li, Shun
AU - Qiu, Na
AU - Zhou, Chao
AU - Ni, Andrew
AU - Sun, Ping
AU - Liu, Jia‐Jun
AU - Huang, Xin‐Lei
AU - Xiong, Tian‐Qing
AU - Zhang, Yu‐Chi
AU - Liu, Hai‐Zhou
AU - Xu, Xiao‐Tao
AU - Wang, Rui
AU - Zhang, Shi‐Qing
AU - Zhang, Yu‐Xin
AU - Liu, Silvia
AU - Dixon, C Edward
AU - Chen, Jun
AU - Yin, Ke‐Jie
TI - Endothelial miR-15a/16-1 Regulation of SYNE1 Mediates Structural and Functional Recovery after Traumatic Brain Injury
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/08/12
SP - e77111
SN - 2198-3844
PB - Wiley
DO - 10.1002/advs.77111
UR - https://doi.org/10.1002/advs.77111
LA - en
ER -

CSL-JSON

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