Evidence map›Paper›PMID 35297562›Full record

ArticleClinical and translational medicine2022

Histone methyltransferase Smyd2 contributes to blood-brain barrier breakdown in stroke.

Jinghuan Wang, Wen Zhong, Qianwen Cheng, Chenxi Xiao, Jie Xu, Zhenghua Su, Haibi Su, Xinhua Liu

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

Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

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  17. Epigenetic mechanisms and potential therapeutic targets in stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
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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

8 authors at 1 institution in 1 country.

Jinghuan WangPharmacophenomics Laboratory, Human Phenome Institute, Pharmacy School, Fudan University, Shanghai, China.
Wen ZhongPharmacophenomics Laboratory, Human Phenome Institute, Pharmacy School, Fudan University, Shanghai, China.
Qianwen ChengPharmacophenomics Laboratory, Human Phenome Institute, Pharmacy School, Fudan University, Shanghai, China.
Chenxi XiaoPharmacophenomics Laboratory, Human Phenome Institute, Pharmacy School, Fudan University, Shanghai, China.
Jie XuPharmacophenomics Laboratory, Human Phenome Institute, Pharmacy School, Fudan University, Shanghai, China.
Zhenghua SuPharmacophenomics Laboratory, Human Phenome Institute, Pharmacy School, Fudan University, Shanghai, China.
Haibi SuPharmacophenomics Laboratory, Human Phenome Institute, Pharmacy School, Fudan University, Shanghai, China.
Xinhua LiuPharmacophenomics Laboratory, Human Phenome Institute, Pharmacy School, Fudan University, Shanghai, China.ORCID 0000-0002-9972-8215
Fudan University · CN

Funding

Shanghai Municipal Science and Technology Major Project 2017SHZDZX01
6 · The paper itself

Abstract

backgroundThe blood-brain barrier (BBB) plays a principal role in the healthy and diseased central nervous systems, and BBB disruption after ischaemic stroke is responsible for increased mortality. Smyd2, a member of the SMYD-methyltransferase family, plays a vital role in disease by methylation of diverse substrates; however, little is known about its role in the pathophysiology of the brain in response to ischaemia-reperfusion injury.

methodsUsing oxygen glucose deprivation and reoxygenation (OGD/R)-induced primary brain microvascular endothelial cells (BMECs) and Smyd2 knockdown mice subjected to middle cerebral artery occlusion, we evaluated the role of Smyd2 in BBB disruption. We performed loss-of-function and gain-of-function studies to investigate the biological function of Smyd2 in ischaemic stroke.

resultsWe found that Smyd2 was a critical factor for regulating brain endothelial barrier integrity in ischaemia-reperfusion injury. Smyd2 is upregulated in peri-ischaemic brains, leading to BBB disruption via methylation-mediated Sphk/S1PR. Knockdown of Smyd2 in mice reduces BBB permeability and improves functional recovery. Using OGD/R-induced BMECs, we demonstrated that Sphk/S1PR methylation modification by Smyd2 affects ubiquitin-dependent degradation and protein stability, which may disrupt endothelial integrity. Moreover, overexpression of Smyd2 can damage endothelial integrity through Sphk/S1PR signalling.

conclusionsOverall, these results reveal a novel role for Smyd2 in BBB disruption in ischaemic stroke, suggesting that Smyd2 may represent a new therapeutic target for ischaemic stroke.

Indexed as

Brain IschemiaIschemic StrokeReperfusion InjuryStrokeAnimalsBlood-Brain BarrierEndothelial CellsGlucoseHistone-Lysine N-MethyltransferaseHistone MethyltransferasesMiceOxygenGlucoseHistone-Lysine N-MethyltransferaseHistone MethyltransferasesOxygenSmyd2 protein, mouseblood-brain barrierbrain microvascular endothelial cellsischaemia strokeSmyd2

Identifiers

PMID35297562
PMCPMC8926904
OpenAlexW4220666838

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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.