Evidence map›Paper›PMID 36915206›Full record

ArticleCell & bioscience2023

Exosomal USP13 derived from microvascular endothelial cells regulates immune microenvironment and improves functional recovery after spinal cord injury by stabilizing IκBα.

Xuhui Ge, Zheng Zhou, Siting Yang, Wu Ye, Zhuanghui Wang, Jiaxing Wang, Chenyu Xiao, Min Cui, Jiawen Zhou, Yufeng Zhu and 7 more

Full text read
In one paragraph

Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Article
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  5. Extracellular vesicle-based therapeutic strategies for spinal cord injury.Extracellular vesicles and circulating nucleic acids · 2026
    Review
  6. Article
  7. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Xuhui Ge *Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Zheng Zhou *Department of Emergency Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Siting Yang *Department of Anesthesiology and Nursing, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Wu YeDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Zhuanghui WangDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Jiaxing WangDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Chenyu XiaoDepartment of Human Anatomy, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
Min CuiDepartment of Human Anatomy, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
Jiawen ZhouDepartment of Pharmacology, China Pharmaceutical University, Nanjing, 211198, China.
Yufeng ZhuDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Rixiao WangDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Yu GaoDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Haofan WangDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Pengyu TangDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Xuhui ZhouDepartment of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.
Ce WangDepartment of Orthopedics, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China. cowwang_111@163.com.
Weihua CaiDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. caiwhspine@njmu.edu.cn.

Funding

Natural Science Foundation of Jiangsu Basic Research Program-Youth Fund Project BK20220734Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University PY2021030
6 · The paper itself

Abstract

Spinal cord injury (SCI) can result in irreversible sensory and motor disability with no effective treatment currently. After SCI, infiltrated macrophages accumulate in epicenter through destructed blood-spinal cord barrier (BSCB). Further, great majority of macrophages are preferentially polarized to M1 phenotype, with only a few transient M2 phenotype. The purpose of this study was to explore roles of vascular endothelial cells in microglia/macrophages polarization and the underlying mechanism. Lipopolysaccharide (LPS) was used to pretreat BV2 microglia and RAW264.7 macrophages followed by administration of conditioned medium from microvascular endothelial cell line bEnd.3 cells (ECM). Analyses were then performed to determine the effects of exosomes on microglia/macrophages polarization and mitochondrial function. The findings demonstrated that administration of ECM shifted microglia/macrophages towards M2 polarization, ameliorated mitochondrial impairment, and reduced reactive oxygen species (ROS) production in vitro. Notably, administration of GW4869, an exosomal secretion inhibitor, significantly reversed these observed benefits. Further results revealed that exosomes derived from bEnd.3 cells (Exos) promote motor rehabilitation and M2 polarization of microglia/macrophages in vivo. Ubiquitin-specific protease 13 (USP13) was shown to be significantly enriched in BV2 microglia treated with Exos. USP13 binds to, deubiquitinates and stabilizes the NF-κB inhibitor alpha (IκBα), thus regulating microglia/macrophages polarization. Administration of the selective IκBα inhibitor betulinic acid (BA) inhibited the beneficial effect of Exos in vivo. These findings uncovered the potential mechanism underlying the communications between vascular endothelial cells and microglia/macrophages after SCI. In addition, this study indicates exosomes might be a promising therapeutic strategy for SCI treatment.

Indexed as

ExosomesMicroglia/macrophages polarizationMitochondriaSpinal cord injuryUSP13/ IκBα

Identifiers

PMID36915206
PMCPMC10012460

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.