Evidence map›Paper›PMID 39118388›Full record

ArticleBritish journal of pharmacology2024

The protein disulfide isomerase A3 and osteopontin axis promotes influenza-induced lung remodelling.

Amit Kumar, Zoe F Mark, Morgan P Carbajal, Dhemerson Souza DeLima, Nicolas Chamberlain, Joseph Walzer, Mona Ruban, Ravishankar Chandrasekaran, Nirav Daphtary, Minara Aliyeva and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2024. 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
–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

3 citing papers in PubMed.

  1. Article
  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

18 authors.

Amit KumarDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Zoe F MarkDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Morgan P CarbajalDivision of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Dhemerson Souza DeLimaDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Nicolas ChamberlainDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Joseph WalzerDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Mona RubanDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Ravishankar ChandrasekaranDivision of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Nirav DaphtaryDivision of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Minara AliyevaDivision of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Matthew E PoynterDivision of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Yvonne M W Janssen-HeiningerDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
Jason H BatesDivision of Pulmonary Disease and Critical Care Medicine, Department of Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.
John F AlcornDivision of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Clemente J BrittoDepartment of Pulmonary, Critical Care and Sleep Medicine, Yale University, New Haven, Connecticut, USA.
Charles S Dela CruzDepartment of Pulmonary, Critical Care and Sleep Medicine, Yale University, New Haven, Connecticut, USA.
Anil G JeggaDivision of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Vikas AnathyDepartment of Pathology and Laboratory Medicine, Larner College of Medicine, The University of Vermont, Burlington, Vermont, USA.

Funding

S-glutathionylation chemistry in fibrotic lung remodelingR35HL135828 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI JANSSEN-HEININGER, YVONNE M. W. · 2017 to 2023
$6.5M
Obese Allergic Asthma and the Impact of Weight Loss on Airway Epithelial FunctionR01HL133920 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI DIXON, ANNE E, POYNTER, MATTHEW E · 2016 to 2020
$3.9M
Mitochondrial Redox Perturbations in Obese Allergic AsthmaR01HL136917 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI ANATHY, VIKAS, DIXON, ANNE E · 2018 to 2022
$3.6M
Endoplasmic Reticulum Stress Signaling in Allergen-induced Airway RemodelingR01HL122383 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI ANATHY, VIKAS · 2015 to 2023
$3.5M
Ketone Body Supplementation in Obese AsthmaR01HL142081 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI POYNTER, MATTHEW E · 2018 to 2021
$1.8M
Unfolded protein response in Influenza virus infection and inflammationR01HL141364 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI ANATHY, VIKAS · 2019 to 2022
$1.6M
Preclinical characterization of saracatinib for cystic fibrosis therapyUG3TR002612 · NCATS · CINCINNATI CHILDRENS HOSP MED CTR · PI CLANCY, JOHN PAUL, JEGGA, ANIL · 2018 to 2019
$636k
Endoplasmic Reticulum (ER)-phagy in Influenza InfectionR21AI183025 · NIAID · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI ANATHY, VIKAS · 2025 to 2025
$433k
NCATS NIH HHS UG3 TR002612NHLBI NIH HHS R01 HL122383NHLBI NIH HHS R01 HL133920NHLBI NIH HHS R01 HL136917NHLBI NIH HHS R01 HL141364NHLBI NIH HHS R01 HL142081NHLBI NIH HHS R35 HL135828NIAID NIH HHS R21 AI183025NIH HHS 1UG3TR002612NIH HHS HL133920NIH HHS HL136917NIH HHS HL141364NIH HHS R01 HL122383NIH HHS R01 HL142081NIH HHS R35 HL135828
6 · The paper itself

Abstract

background and purposeFibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral-fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza-induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral-mediated fibrotic remodelling. EXPERIMENTAL APPROACH: A retrospective analysis of TriNetX data sets was conducted. Serum from healthy controls and influenza A virus (IAV)-infected patients was analysed. An inhibitor of PDIA3, punicalagin, and a neutralizing antibody for SPP1 were administered in mice. Macrophage cells treated with macrophage colony-stimulating factor (M-CSF) were used as a cell culture model. KEY

resultsThe TriNetX data set showed an increase in lung fibrosis and decline in lung function in flu-infected acute respiratory distress syndrome (ARDS) patients compared with non-ARDS patients. Serum samples revealed a significant increase in SPP1 and PDIA3 in influenza-infected patients. Lung PDIA3 and SPP1 expression increased following viral infection in mouse models. Punicalagin administration 2 weeks after IAV infection in mice caused a significant decrease in lung fibrosis and improved oxygen saturation. Administration of neutralizing SPP1 antibody decreased lung fibrosis. Inhibition of PDIA3 decreased SPP1secretion from macrophages, in association with diminished disulfide bonds in SPP1. CONCLUSION AND IMPLICATIONS: The PDIA3-SPP1 axis promotes post-influenza lung fibrosis in mice and that pharmacological inhibition of PDIA3 or SPP1 can treat virus-induced lung fibrotic sequela.

Indexed as

LungOsteopontinProtein Disulfide-IsomerasesAnimalsFemaleHumansHydrolyzable TanninsInfluenza, HumanMaleMiceMice, Inbred C57BLMiddle AgedOrthomyxoviridae InfectionsPulmonary FibrosisRetrospective StudiesHydrolyzable TanninsOsteopontinPDIA3 protein, humanPdia3 protein, mouseProtein Disulfide-IsomerasesAHRinfluenzalung fibrosislung functionM‐CSFPDIA3SPP1

Identifiers

PMID39118388
PMCPMC12421427

What Socratic holds

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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.