Evidence map›Paper›PMID 31465536›Full record

ArticleBritish journal of pharmacology2020

Silencing of microRNA-494 inhibits the neurotoxic Th1 shift via regulating HDAC2-STAT4 cascade in ischaemic stroke.

Haiping Zhao, Guangwen Li, Rongliang Wang, Zhen Tao, Qingfeng Ma, Sijia Zhang, Ziping Han, Feng Yan, Fangfang Li, Ping Liu and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. CD4Frontiers in immunology · 2025
    Review
  6. MicroRNA Profiles in Critically Ill Patients.Current medicinal chemistry · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
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  16. Review
  17. Article
  18. 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

13 authors at 1 institution in 1 country.

Haiping ZhaoInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Guangwen LiInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Rongliang WangInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Zhen TaoInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Qingfeng MaInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Sijia ZhangInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Ziping HanInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Feng YanInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Fangfang LiInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Ping LiuInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Shubei MaInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Xunming JiInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Yumin LuoInstitute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.ORCID 0000-0002-2712-8974
Capital Medical University · CN

Funding

Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education KZ201810025041Distinguished Professor of Cheung Kong Scholars Program T2014251National Natural Science Foundation of China 81771412National Natural Science Foundation of China 81771413, 81571280
6 · The paper itself

Abstract

background and purposeT helper cell 1 (Th1)-skewed neurotoxicity contributes to the poor outcome of stroke in rodents. Here, we have elucidated the mechanism of the Th1/Th2 shift in acute ischaemic stroke (AIS) patients at hyperacute phase and have looked for a miRNA-based therapeutic target. EXPERIMENTAL APPROACH: MiR-494 levels in blood from AIS patients and controls were measured by real-time PCR. C57BL/6J mice were subjected to transient middle cerebral artery occlusion, and cortical neurons were subjected to oxygen-glucose deprivation. Luciferase reporter system, chromatin immunoprecipitation sequencing (ChIP-Seq), and ChIP-PCR were used to uncover possible mechanisms. KEY

resultsIn lymphocytes from AIS patients, there was a Th1/Th2 shift and histone deacetylase 2 (HDAC2) was markedly down-regulated. ChIP-seq showed that HDAC2 binding sites were enriched in regulation of Th1 cytokine production, and ChIP-PCR confirmed that HDAC2 binding was changed at the intron of STAT4 and the promoter of T-box transcription factor 21 (T-bet) in lymphocytes from AIS patients. MiR-494 was the most significantly increased miRNA in lymphocytes from AIS patients, and miR-494-3p directly targeted HDAC2. A strong association existed between miR-494 and Th1 cytokines, and neurological deficit as measured by the National Institute of Health Stroke Scale (NIHSS) in AIS patients. In vitro and in vivo experiments showed that antagomir-494 reduced Th1 shift-mediated neuronal and sensorimotor functional damage in the mouse model of ischaemic stroke, via the HDAC2-STAT4 pathway. CONCLUSION AND IMPLICATIONS: We demonstrated that miR-494 inhibition prevented Th1-skewed neurotoxicity through regulation of the HDAC2-STAT4 cascade.

Indexed as

AgedAnimalsAntagomirsFemaleHistone Deacetylase 2HumansIschemic StrokeJurkat CellsMaleMiceMice, Inbred C57BLMicroRNAsMiddle AgedSTAT4 Transcription FactorTh1 CellsAntagomirsHdac2 protein, mouseHistone Deacetylase 2MicroRNAsMirn494 microRNA, mouseStat4 protein, mouseSTAT4 Transcription Factor

Identifiers

PMID31465536
PMCPMC6976789
OpenAlexW2970212843

What OpenQuestion holds

Textmetadata
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.