Evidence map›Paper›PMID 37032635›Full record

ArticleCNS neuroscience & therapeutics2023

Inhibition of TANK-binding kinase1 attenuates the astrocyte-mediated neuroinflammatory response through YAP signaling after spinal cord injury.

Wenbin Zhang, Mengxian Jia, Jiashu Lian, Sheng Lu, Jian Zhou, Ziwei Fan, Zhoule Zhu, Yaozhi He, Changgang Huang, Mingyu Zhu and 4 more

Open access · goldAbstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
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

12 citing papers in PubMed, 12 citations in OpenAlex.

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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

14 authors at 3 institutions in 1 country.

Wenbin ZhangDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Mengxian JiaDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jiashu LianDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Sheng LuDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jian ZhouDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Ziwei FanDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zhoule ZhuDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yaozhi HeDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Changgang HuangSchool of Pharmacy, and Department of Neurosurgery, The Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Mingyu ZhuDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0000-0002-9373-6871
Jian WangCenter for Wound Repair and Regeneration, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Ying WangDepartment of Clinical Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Zhihui HuangDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0000-0001-9910-0228
Honglin TengDepartment of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID 0000-0003-0700-7574
Wenzhou Medical University · CNAffiliated Hospital of Hangzhou Normal University · CNHangzhou First People's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsTANK-binding kinase 1 (TBK1) is involved in regulating the pathological process of a variety of inflammatory diseases in the central nervous system. However, its role and underlying molecular mechanisms in spinal cord injury (SCI) remain largely unknown.

methodsWe employed the TBK1 inhibitor amlexanox (ALX) to address this question. An in vivo clip-compressive SCI model and in vitro lipopolysaccharide (LPS)-induced astrocyte inflammation model were established to examine the effects of TBK1 inhibition on the expression of proinflammatory cytokines.

resultsIn this study, we found that TBK1 and TBK1-medicated innate immune pathways, such as TBK1/IRF3 and noncanonical NF-κB signaling, were activated in astrocytes and neurons after SCI. Furthermore, inhibition of TBK1 by ALX alleviated neuroinflammation response, reduced the loss of motor neurons, and improved the functional recovery after SCI. Mechanistically, inhibition of TBK1 activity promoted the activation of the noncanonical NF-κB signaling pathway and inhibited p-IRF3 activity in LPS-induced astrocytes, and the TBK1 activity was required for astrocytic activation through yes-associated protein (YAP) signaling after SCI and in LPS-induced astrocytes inflammation model.

conclusionTBK1-medicated innate immune pathway in astrocytes through YAP signaling plays an important role in the pathogenesis of SCI and inhibition of TBK1 may be a potential therapeutic drug for SCI.

Indexed as

NF-kappa BProtein Serine-Threonine KinasesSpinal Cord InjuriesYAP-Signaling ProteinsAnimalsAstrocytesInflammationLipopolysaccharidesSignal TransductionSpinal CordLipopolysaccharidesNF-kappa BProtein Serine-Threonine KinasesYAP-Signaling Proteinsamlexanoxastrocytesnoncanonical NF-κB signaling pathwayspinal cord injuryTBK1YAP

Identifiers

PMID37032635
PMCPMC10352897
OpenAlexW4363645809

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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.