Endothelial miR‐15a/16‐1 Regulation of SYNE1 Mediates Structural and Functional Recovery after Traumatic Brain Injury
7 affiliations
- 1Department of Neurology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA
- 2Geriatric Research, Education and Clinical Center Veterans Affairs Pittsburgh Healthcare System Pittsburgh Pennsylvania USA
- 3Warren Alpert Medical School Brown University Providence Rhode Island USA
- 4Pittsburgh Liver Research Center University of Pittsburgh Pittsburgh Pennsylvania USA
- 5Organ Pathobiology and Therapeutics Institute University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA
- 6Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA
- 7Department of Neurosurgery University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA
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.
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BibTeX
@article{li2026endothelial,
title = {{Endothelial miR‐15a/16‐1 Regulation of SYNE1 Mediates Structural and Functional Recovery after Traumatic Brain Injury}},
author = {Shun Li and Na Qiu and Chao Zhou and Andrew Ni and Ping Sun and Jia‐Jun Liu and Xin‐Lei Huang and Tian‐Qing Xiong and Yu‐Chi Zhang and Hai‐Zhou Liu and Xiao‐Tao Xu and Rui Wang and Shi‐Qing Zhang and Yu‐Xin Zhang and Silvia Liu and C. Edward Dixon and Jun Chen and Ke‐Jie Yin},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.77111},
url = {https://doi.org/10.1002/advs.77111},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Endothelial miR‐15a/16‐1 Regulation of SYNE1 Mediates Structural and Functional Recovery after Traumatic Brain Injury
AU - Shun Li
AU - Na Qiu
AU - Chao Zhou
AU - Andrew Ni
AU - Ping Sun
AU - Jia‐Jun Liu
AU - Xin‐Lei Huang
AU - Tian‐Qing Xiong
AU - Yu‐Chi Zhang
AU - Hai‐Zhou Liu
AU - Xiao‐Tao Xu
AU - Rui Wang
AU - Shi‐Qing Zhang
AU - Yu‐Xin Zhang
AU - Silvia Liu
AU - C. Edward Dixon
AU - Jun Chen
AU - Ke‐Jie Yin
PY - 2026
DA - 2026/08/12
JO - Advanced Science
DO - 10.1002/advs.77111
UR - https://doi.org/10.1002/advs.77111
AB - 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.
SN - 2198-3844
ER -