Evidence map›Paper›PMID 38816442›Full record

ArticlePediatric research2024

Experimental congenital diaphragmatic hernia features an alteration of DNA sensing targets cGAS and STING.

Moritz Markel, Wai Hei Tse, Nolan De Leon, Marietta Jank, Jaida Albrechtsen, Shana Kahnamoui Zadeh, Daywin Patel, Arzu Ozturk, Martin Lacher, Richard Wagner and 1 more

Abstract read
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Article in Pediatric research, 2024. 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

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.

  1. 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

11 authors.

Moritz MarkelDepartment of Pediatric Surgery, University of Leipzig, Leipzig, Germany.
Wai Hei TseDivision of Pediatric Surgery, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Nolan De LeonDivision of Pediatric Surgery, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Marietta JankDivision of Pediatric Surgery, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Jaida AlbrechtsenDivision of Pediatric Surgery, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Shana Kahnamoui ZadehDivision of Pediatric Surgery, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Daywin PatelDivision of Pediatric Surgery, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Arzu OzturkDivision of Pediatric Surgery, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Martin LacherDepartment of Pediatric Surgery, University of Leipzig, Leipzig, Germany.
Richard WagnerDepartment of Pediatric Surgery, University of Leipzig, Leipzig, Germany.
Richard KeijzerDivision of Pediatric Surgery, Departments of Surgery, Pediatrics & Child Health and Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, and Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. rkeijzer@hsc.mb.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe pathogenesis of congenital diaphragmatic hernia (CDH) depends on multiple factors. Activation of the DNA-sensing cyclic-GMP-AMP-synthase (cGAS) and Stimulator-of-Interferon-Genes (STING) pathway by double-stranded DNA (dsDNA) links environmental stimuli and inflammation. We hypothesized that nitrofen exposure alters cGAS and STING in human bronchial epithelial cells and fetal rat lungs.

methodsWe used the Quant-IT™-PicoGreen™ assay to assess dsDNA concentration in BEAS-2B cells after 24 h of nitrofen-exposure and performed immunofluorescence of cGAS/STING. We used nitrofen to induce CDH and harvested control and CDH lungs at embryonic day E15, E18 and E21 for cGAS/STING immunofluorescence, RT-qPCR and RNA-Scope™ in-situ-hybridization (E18, E21).

resultsWe found a higher concentration of dsDNA following nitrofen treatment. Nitrofen-exposure to BEAS-2B cells increased cGAS and STING protein abundance. cGAS abundance was higher in nitrofen lungs at E15, E18 and E21. RNA-Scope in-situ-hybridization showed higher cGAS and STING expression in E18 and E21 lungs. RT-qPCR revealed higher mRNA expression levels of STING in E21 nitrofen-induced lungs.

conclusionOur data suggest that nitrofen-exposure increases dsDNA content which leads to stimulation of the cGAS/STING pathway in human BEAS-2B cells and the nitrofen rat model of CDH. Consequently, DNA sensing and the cGAS-STING-pathway potentially contribute to abnormal lung development in CDH. IMPACT STATEMENT: We found an alteration of DNA sensing targets cGAS and STING in human BEAS-2B cells and experimental congenital diaphragmatic hernia with higher protein abundance and mRNA expression in cells and lung sections of nitrofen-treated rat pups. This is the first study to investigate DNA sensing, a potential link between environmental stimuli and inflammation, in experimental CDH. Our study extends the knowledge on the pathogenesis of experimental CDH.

Indexed as

DNAHernias, Diaphragmatic, CongenitalMembrane ProteinsNucleotidyltransferasesAnimalsCell LineCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDisease Models, AnimalEpithelial CellsFemaleHumansLungPhenyl EthersRatsSignal TransductionSTING ProteincGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNAMembrane ProteinsnitrofenNucleotidyltransferasesPhenyl EthersSTING1 protein, humanSTING Protein

Identifiers

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Textmetadata
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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 Socratic graph.