Evidence map›Paper›PMID 36055408›Full record

ArticleThe Journal of biological chemistry2022

Ubiquitin ligase Triad1 promotes neurite outgrowth by inhibiting MDM2-mediated ubiquitination of the neuroprotective factor pleiotrophin.

Chunshuai Wu, Guanhua Xu, Guofeng Bao, Hong Gao, Jiajia Chen, Jinlong Zhang, Chu Chen, Hongxiang Hong, Pengfei Xue, Jiawei Jiang and 6 more

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

Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 51% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
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

16 authors at 2 institutions in 1 country.

Chunshuai WuDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China; Key Laboratory for Restoration Mechanism and Clinical Translation of Spinal Cord Injury, Nantong, China; Research Institute for Spine and Spinal Cord Disease of Nantong University, Nantong, China.
Guanhua XuDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Guofeng BaoDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Hong GaoDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Jiajia ChenDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Jinlong ZhangDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Chu ChenDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Hongxiang HongDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Pengfei XueDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Jiawei JiangDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Yang LiuDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Jiayi HuangDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Yue SunDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Jiawei FuDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Yiqiu LiDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China.
Zhiming CuiDepartment of Spine Surgery, The Affiliated Hospital 2 of Nantong University, The First People's Hospital of Nantong, Nantong, China; Key Laboratory for Restoration Mechanism and Clinical Translation of Spinal Cord Injury, Nantong, China; Research Institute for Spine and Spinal Cord Disease of Nantong University, Nantong, China. Electronic address: zhimingcuispine@163.com.
Affiliated Hospital of Nantong University · CNNantong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spinal cord injury (SCI) is the most severe result of spine injury, but no effective therapy exists to treat SCI. We have previously shown that the E3 ubiquitin ligase Two RING fingers and DRIL 1 (Triad1) promotes neurite outgrowth after SCI. However, the mechanism by which Triad1 affects neuron growth and the potential involvement of its ubiquitination activity is unclear. Neuroprotective cytokine pleiotrophin (PTN) can promote microglia proliferation and neurotrophic factor secretion to achieve neuroprotection. We find using immunostaining and behavioral assays in rats that the expression of Triad1 and the PTN was peaked at 1 day after SCI and Triad1 improved motor function and histomorphological injury after SCI. We show using flow cytometry and astrocyte/neuronal coculture assays that Triad1 overexpression promoted PTN protein levels, neurotrophic growth factor (NGF) expression, brain-derived neurotrophic factor (BDNF) expression, astrocyte and neuronal viability, and neurite outgrowth but suppressed astrocyte apoptosis, while shRNA-mediated knockdown of Triad1 and PTN had the opposite effects. Ubiquitin ligase murine double mutant 2 (MDM2) has previously been demonstrated to participate in the process of neurite outgrowth and mediate ubiquitination of p53. Furthermore, we demonstrate overexpression of MDM2 downregulated PTN protein levels, NGF expression and BDNF expression in astrocytes, and inhibited neurite outgrowth of neurons. In addition, MDM2 facilitated PTN ubiquitination, which was reversed by Triad1. Finally, we show simultaneous sh-PTN and MDM2 overexpression attenuated the neurite outgrowth-promoting effect of Triad1 overexpression. In conclusion, we propose Triad1 promotes astrocyte-dependent neurite outgrowth to accelerate recovery after SCI by inhibiting MDM2-mediated PTN ubiquitination.

Indexed as

Spinal Cord InjuriesUbiquitinAnimalsBrain-Derived Neurotrophic FactorCarrier ProteinsCytokinesGene ExpressionMiceNerve Growth FactorNeuritesNeuronal OutgrowthNeuroprotectionRatsUbiquitinationUbiquitin-Protein LigasesArih2 protein, ratBrain-Derived Neurotrophic FactorCarrier ProteinsCytokinesNerve Growth FactorpleiotrophinUbiquitinUbiquitin-Protein LigasesMDM2neurite outgrowthPTNspinal cord injuryTriad1

Identifiers

PMID36055408
PMCPMC9531182
OpenAlexW4293722464

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.