Evidence map›Paper›PMID 37876037›Full record

ArticleClinical and translational allergy2023

Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity.

Michael A Portelli, Sangita Bhaker, Vincent Pang, David O Bates, Simon R Johnson, Andrew P Mazar, Dominick Shaw, Christopher Brightling, Ian Sayers

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

Article in Clinical and translational allergy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 23% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
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

9 authors at 3 institutions in 2 countries.

Michael A PortelliCentre for Respiratory Research, NIHR Respiratory Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.ORCID https://orcid.org/0000-0003-0821-4575
Sangita BhakerCentre for Respiratory Research, NIHR Respiratory Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.
Vincent PangTumour Vascular Biology Group, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.
David O BatesTumour Vascular Biology Group, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.ORCID https://orcid.org/0000-0003-4850-2360
Simon R JohnsonCentre for Respiratory Research, NIHR Respiratory Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.
Andrew P MazarDepartment of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Dominick ShawCentre for Respiratory Research, NIHR Respiratory Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.
Christopher BrightlingDepartment of Respiratory Medicine, University of Leicester, University Hospitals of Leicester NHS Trust, Leicester, UK.
Ian SayersCentre for Respiratory Research, NIHR Respiratory Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, UK.
University of Nottingham · GBNorthwestern University · USUniversity of Leicester · GB

Funding

British Heart Foundation BHF PG/13/85/30536Medical Research CouncilWellcome Trust 225221
6 · The paper itself

Abstract

backgroundExpression of the urokinase plasminogen activator receptor (uPAR) is elevated in the airway epithelium in asthma; however, the contribution of uPAR to asthma pathogenesis and scope for therapeutic targeting remains unknown.

objectivesTo determine (i) the expression profile of uPAR in cultured human bronchial epithelial cells (HBEC) from asthma patients, (ii) the relationship between uPAR and the epithelial barrier, including blocking uPAR functions and (iii) the function of different uPAR isoforms.

methodsuPAR levels in HBECs isolated from asthma patients and cells at air liquid interface (ALI) during differentiation were quantified. Transepithelial electrical resistance or electrical cell impedance sensing was used to relate uPAR levels to barrier properties, including effects of uPAR blocking antibodies. The functional effects of gain of function was determined using transcriptomics, in cells over-expressing membrane (muPAR), soluble cleaved (scuPAR) or soluble spliced (ssuPAR) isoforms.

resultsElevated expression of uPAR was a feature of cultured HBECs from asthma patients, suggesting intrinsic alterations in asthma patient cells. Soluble uPAR levels inversely correlated with barrier properties of the HBEC layer in 2D and ALI. Blocking uPAR-integrin interactions enhanced barrier formation. The gain of function cells showed limited transcriptomic changes.

conclusionThis study provides a significant advance in our understanding of the relationship between asthma, uPAR and the epithelial barrier, where elevated circulating uPAR results in a reduced cell barrier, a phenotype prevalent in asthma.

Indexed as

asthmabarrierbronchial epithelial cellsurokinase plasminogen receptor

Identifiers

PMID37876037
PMCPMC10542610
OpenAlexW4387229626

What OpenQuestion holds

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LicenceCC BY
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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.