Evidence map›Paper›PMID 32546573›Full record

ArticleThorax2020

Mesenchymal stromal/stem cells modulate response to experimental sepsis-induced lung injury via regulation of miR-27a-5p in recipient mice.

Nadim Younes, Louis Zhou, Hajera Amatullah, Shirley H J Mei, Raquel Herrero, Jose Angel Lorente, Duncan J Stewart, Philip Marsden, W Conrad Liles, Pingzhao Hu and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Thorax, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
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  10. MicroRNA Profiles in Critically Ill Patients.Current medicinal chemistry · 2024
    Review
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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 at 5 institutions in 3 countries.

Nadim Younes *Critical Care Medicine, The Keenan Research Centre for Biomedical Science of Saint Michael's Hospital, Toronto, Ontario, Canada.
Louis Zhou *Critical Care Medicine, The Keenan Research Centre for Biomedical Science of Saint Michael's Hospital, Toronto, Ontario, Canada.
Hajera AmatullahCritical Care Medicine, The Keenan Research Centre for Biomedical Science of Saint Michael's Hospital, Toronto, Ontario, Canada.
Shirley H J MeiOttawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Raquel HerreroCritical Care Service, Hospital Universitario de Getafe-CIBER de Enfermedades Respiratorias (CIBERES), Getafe, Spain.ORCID 0000-0001-8789-0904
Jose Angel LorenteCritical Care Service, Hospital Universitario de Getafe-CIBER de Enfermedades Respiratorias (CIBERES), Getafe, Spain.
Duncan J StewartOttawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Philip MarsdenCritical Care Medicine, The Keenan Research Centre for Biomedical Science of Saint Michael's Hospital, Toronto, Ontario, Canada.
W Conrad LilesDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Pingzhao HuDepartment of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
Claudia C Dos SantosCritical Care Medicine, The Keenan Research Centre for Biomedical Science of Saint Michael's Hospital, Toronto, Ontario, Canada dossantosC@smh.ca.
St. Michael's Hospital · CACentro de Investigación Biomédica en Red de Enfermedades Respiratorias · ESUniversity of Ottawa · CAUniversity of Manitoba · CAUniversity of Washington · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionMesenchymal stromal cell (MSC) therapy mitigates lung injury and improves survival in murine models of sepsis. Precise mechanisms of therapeutic benefit remain poorly understood.

objectivesTo identify host-derived regulatory elements that may contribute to the therapeutic effects of MSCs, we profiled the microRNAome (miRNAome) and transcriptome of lungs from mice randomised to experimental polymicrobial sepsis-induced lung injury treated with either placebo or MSCs. METHODS AND

resultsA total of 11 997 genes and 357 microRNAs (miRNAs) expressed in lungs were used to generate a statistical estimate of association between miRNAs and their putative mRNA targets; 1395 miRNA:mRNA significant association pairs were found to be differentially expressed (false discovery rate ≤0.05). MSC administration resulted in the downregulation of miR-27a-5p and upregulation of its putative target gene VAV3 (adjusted p=1.272E-161) in septic lungs. In human pulmonary microvascular endothelial cells, miR-27a-5p expression levels were increased while VAV3 was decreased following lipopolysaccharide (LPS) or tumour necrosis factor (TNF) stimulation. Transfection of miR-27a-5p mimic or inhibitor resulted in increased or decreased VAV3 message, respectively. Luciferase reporter assay demonstrated specific binding of miR-27a-5p to the 3'UTR of VAV3. miR27a-5p inhibition mitigated TNF-induced (1) delayed wound closure, increased (2) adhesion and (3) transendothelial migration but did not alter permeability. In vivo, cell infiltration was attenuated by intratracheal coinstillation of the miR-27a-5p inhibitor, but this did not protect against endotoxin-induced oedema formation.

conclusionsOur data support involvement of miR-27a-5p and VAV3 in cellular adhesion and infiltration during acute lung injury and a potential role for miR-27a-based therapeutics for acute respiratory distress syndrome.

Indexed as

Gene Expression RegulationAcute Lung InjuryAnimalsApoptosisCells, CulturedDisease Models, AnimalMaleMesenchymal Stem Cell TransplantationMiceMice, Inbred C57BLMicroRNAsRNA, MessengerSepsisSignal TransductionMicroRNAsMirn27 microRNA, mouseRNA, MessengerARDScritical carerespiratory infection

Identifiers

PMID32546573
PMCPMC7361025
OpenAlexW3034481106

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.