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ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Dnmt1 Alleviates S1PR1-Mediated Pyroptosis after Spinal Cord Injury through Regulating Pon3 Expression.

Birong Peng, Haolong Lin, Mi Zhang, Wenhao Kuang, Jiaqi Zhang, Shuai Wang, Yuanfang Sun, Wenning Xu, Lixin Zhu

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. 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
–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

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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.

  1. Article
  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

9 authors.

Birong PengDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.ORCID https://orcid.org/0009-0006-8673-476X
Haolong LinDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Mi ZhangDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Wenhao KuangDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Jiaqi ZhangDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Shuai WangDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Yuanfang SunDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Wenning XuDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.ORCID https://orcid.org/0000-0002-4520-3827
Lixin ZhuDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.ORCID https://orcid.org/0000-0003-3055-3063

Funding

National Natural Science Foundation of China 82302721Natural Science Foundation of Guangdong Province 2024A1515013023
6 · The paper itself

Abstract

Spinal cord injury (SCI), as a severe neurological disorder, remains a formidable challenge in clinical treatment. Pyroptosis-triggered neuroinflammation exacerbates secondary damage, neuronal death, and impairs recovery after SCI, making it a critical pathological factor. However, the exact pathophysiological mechanisms are incompletely understood. In this study, bioinformatics tools are first employed to identify key targets associated with SCI. Subsequent western blot and immunofluorescence assays reveal a time-dependent decrease in Pon3 expression, which is predominantly localized in neuronal cells. Conversely, Dnmt1 expression shows a progressive increase following SCI. By constructing a Pon3-overexpressing virus, it is demonstrated that Pon3 overexpression mitigates pyroptosis in rat and PC12 cells. This process promotes autophagy, significantly improving the prognosis of SCI in rats. Moreover, it enhances the survival rate of PC12 cells. mRNA sequencing and follow-up experiments revealed that Pon3 inhibits the downstream target S1PR1, promotes autophagy, and thereby suppresses pyroptosis. Additionally, through the use of a Dnmt1 inhibitor and the knockout of the Pon3 gene, it is shown that Dnmt1 alleviates SCI-induced pyroptosis by modulating Pon3 expression. Collectively, this work reveals that Dnmt1 alleviates S1PR1-mediated pyroptosis following SCI via regulating Pon3 expression.

Indexed as

DNA (Cytosine-5-)-Methyltransferase 1PyroptosisSphingosine-1-Phosphate ReceptorsSpinal Cord InjuriesAnimalsAutophagyDisease Models, AnimalMalePC12 CellsRatsRats, Sprague-DawleyDNA (Cytosine-5-)-Methyltransferase 1Dnmt1 protein, ratSphingosine-1-Phosphate ReceptorsDnmt1Pon3pyroptosisS1PR1spinal cord injury

Identifiers

PMID40884250
PMCPMC12622493

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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.