Evidence map›Paper›PMID 37848983›Full record

ArticleJournal of translational medicine2023

Neurotrophin-3 promotes peripheral nerve regeneration by maintaining a repair state of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway.

Xiong Xu, Lili Song, Yueying Li, Jin Guo, Shuo Huang, Shuang Du, Weizhen Li, Rangjuan Cao, Shusen Cui

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

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  11. A SynB1-conjugated antibody cocktail crosses the blood-brain barrier to produce a therapeutic effect on rabies.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

9 authors at 3 institutions in 1 country.

Xiong XuDepartment of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, China.
Lili SongDepartment of Hand & Microsurgery, Peking University Shenzhen Hospital, Shenzhen, China.
Yueying LiDepartment of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, China.
Jin GuoDepartment of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, China.
Shuo HuangKey Laboratory of Peripheral Nerve Injury and Regeneration of Jilin Province, Changchun, China.
Shuang DuDepartment of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, China.
Weizhen LiDepartment of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, China.
Rangjuan CaoDepartment of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, China. caorj@jlu.edu.cn.ORCID http://orcid.org/0000-0002-8279-614X
Shusen CuiDepartment of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, China. cuiss@jlu.edu.cn.
Union Hospital · CNCenter for High Pressure Science & Technology Advanced Research · CNPeking University Shenzhen Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMaintaining the repair phenotype of denervated Schwann cells in the injured distal nerve is crucial for promoting peripheral nerve regeneration. However, when chronically denervated, the capacity of Schwann cells to support repair and regeneration deteriorates, leading to peripheral nerve regeneration and poor functional recovery. Herein, we investigated whether neurotrophin-3 (NT-3) could sustain the reparative phenotype of Schwann cells and promote peripheral nerve regeneration after chronic denervation and aimed to uncover its potential molecular mechanisms.

methodsWestern blot was employed to investigate the relationship between the expression of c-Jun and the reparative phenotype of Schwann cells. The inducible expression of c-Jun by NT-3 was examined both in vitro and in vivo with western blot and immunofluorescence staining. A chronic denervation model was established to study the role of NT-3 in peripheral nerve regeneration. The number of regenerated distal axons, myelination of regenerated axons, reinnervation of neuromuscular junctions, and muscle fiber diameters of target muscles were used to evaluate peripheral nerve regeneration by immunofluorescence staining, transmission electron microscopy (TEM), and hematoxylin and eosin (H&E) staining. Adeno-associated virus (AAV) 2/9 carrying shRNA, small molecule inhibitors, and siRNA were employed to investigate whether NT-3 could signal through the TrkC/ERK pathway to maintain c-Jun expression and promote peripheral nerve regeneration after chronic denervation.

resultsAfter peripheral nerve injury, c-Jun expression progressively increased until week 5 and then began to decrease in the distal nerve following denervation. NT-3 upregulated the expression of c-Jun in denervated Schwann cells, both in vitro and in vivo. NT-3 promoted peripheral nerve regeneration after chronic denervation, mainly by upregulating or maintaining a high level of c-Jun rather than NT-3 itself. The TrkC receptor was consistently presented on denervated Schwann cells and served as NT-3 receptors following chronic denervation. NT-3 mainly upregulated c-Jun through the TrkC/ERK pathway.

conclusionNT-3 promotes peripheral nerve regeneration by maintaining the repair phenotype of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway. It provides a potential target for the clinical treatment of peripheral nerve injury after chronic denervation.

Indexed as

Nerve RegenerationNeurotrophin 3Peripheral Nerve InjuriesSchwann CellsAxonsDenervationHumansMAP Kinase Signaling SystemReceptor Protein-Tyrosine KinasesNeurotrophin 3Receptor Protein-Tyrosine KinasesChronic denervationc-JunERK pathwayNeurotrophin-3Peripheral nerve regenerationRepair Schwann cell

Identifiers

PMID37848983
PMCPMC10583391
OpenAlexW4387701224

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.