Evidence map›Paper›PMID 34944023›Full record

ArticleCells2021

The Methyltransferase Smyd1 Mediates LPS-Triggered Up-Regulation of IL-6 in Endothelial Cells.

Ahmed Shamloul, Gustav Steinemann, Kerrin Roos, Celine Huajia Liem, Jonathan Bernd, Thorsten Braun, Andreas Zakrzewicz, Janine Berkholz

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 2 pooled it
0.6field-weighted citation impact, top 35% 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

12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.

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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.

Ahmed ShamloulShear Stress and Vascular Biology Research Group, Institute of Physiology, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Gustav SteinemannShear Stress and Vascular Biology Research Group, Institute of Physiology, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.ORCID 0000-0002-4439-3577
Kerrin RoosShear Stress and Vascular Biology Research Group, Institute of Physiology, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Celine Huajia LiemShear Stress and Vascular Biology Research Group, Institute of Physiology, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Jonathan BerndShear Stress and Vascular Biology Research Group, Institute of Physiology, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Thorsten BraunDepartment of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.ORCID 0000-0002-1989-9920
Andreas ZakrzewiczShear Stress and Vascular Biology Research Group, Institute of Physiology, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Janine BerkholzShear Stress and Vascular Biology Research Group, Institute of Physiology, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.ORCID 0000-0002-0470-6487
Humboldt-Universität zu Berlin · DE

Funding

Deutsche Forschungsgemeinschaft 6697/2-1Sonnenfeld Foundation
6 · The paper itself

Abstract

The lysine methyltransferase Smyd1 with its characteristic catalytic SET-domain is highly enriched in the embryonic heart and skeletal muscles, participating in cardiomyogenesis, sarcomere assembly and chromatin remodeling. Recently, significant Smyd1 levels were discovered in endothelial cells (ECs) that responded to inflammatory cytokines. Based on these biochemical properties, we hypothesized that Smyd1 is involved in inflammation-triggered signaling in ECs and therefore, investigated its role within the LPS-induced signaling cascade. Human endothelial cells (HUVECs and EA.hy926 cells) responded to LPS stimulation with higher intrinsic Smyd1 expression. By transfection with expression vectors containing gene inserts encoding either intact Smyd1, a catalytically inactive Smyd1-mutant or Smyd1-specific siRNAs, we show that Smyd1 contributes to LPS-triggered expression and secretion of IL-6 in EA.hy926 cells. Further molecular analysis revealed this process to be based on two signaling pathways: Smyd1 increased the activity of NF-κB and promoted the trimethylation of lysine-4 of histone-3 (H3K4me3) within the IL-6 promoter, as shown by ChIP-RT-qPCR combined with IL-6-promoter-driven luciferase reporter gene assays. In summary, our experimental analysis revealed that LPS-binding to ECs leads to the up-regulation of Smyd1 expression to transduce the signal for IL-6 up-regulation via activation of the established NF-κB pathway as well as via epigenetic trimethylation of H3K4.

Indexed as

DNA-Binding ProteinsDNA MethylationEndothelial CellsEpigenesis, GeneticGene Expression Regulation, DevelopmentalHumansHuman Umbilical Vein Endothelial CellsInflammationInterleukin-6LipopolysaccharidesMuscle ProteinsNF-kappa BPromoter Regions, GeneticRNA, Small InterferingSignal TransductionTranscription FactorsDNA-Binding ProteinsInterleukin-6LipopolysaccharidesMuscle ProteinsNF-kappa BRNA, Small InterferingSMYD1 protein, humanTranscription Factorsendothelial cellshistone methylationIL-6lipopolysaccharideNF-κBsepsisSmyd1

Identifiers

PMID34944023
PMCPMC8700543
OpenAlexW4200025932

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.