Evidence map›Paper›PMID 37390364›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2023

Role of Extracellular Vesicles in the Propagation of Lung Fibrosis in Systemic Sclerosis.

Joe E Mouawad, Matthew Sanderson, Shailza Sharma, Kristi L Helke, Joseph M Pilewski, Satish N Nadig, Carol Feghali-Bostwick

Open access · bronzeAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

14 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Sex Disparity in Systemic Sclerosis-Associated Pulmonary Fibrosis.International journal of molecular sciences · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Study on the changes of extracellular matrix morphology and components in COPD animal model by using lung decellularized scaffold.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. IGF-II regulates lysyl oxidase propeptide and mediates its effects in part via basic helix-loop-helix E40.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Article
  12. Article
  13. Article
  14. Review
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

7 authors at 3 institutions in 1 country.

Joe E MouawadDivision of Rheumatology & Immunology, Department of Medicine, Medical University of South Carolina and Medical Scientist Training Program, Medical University of South Carolina, Charleston.
Matthew SandersonDivision of Rheumatology & Immunology, Department of Medicine, Medical University of South Carolina, Charleston.
Shailza SharmaDivision of Rheumatology & Immunology, Department of Medicine, Medical University of South Carolina, Charleston.ORCID 0000-0001-5746-1447
Kristi L HelkeDepartments of Comparative Medicine and Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston.
Joseph M PilewskiDivision of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Satish N NadigDivision of Organ Transplantation, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Carol Feghali-BostwickDivision of Rheumatology & Immunology, Department of Medicine, Medical University of South Carolina, Charleston.ORCID 0000-0002-6750-6407
Medical University of South Carolina · USNorthwestern University · USUniversity of Pittsburgh · US

Funding

Pulmonary Focused Foundations in Innovation and Scholarship (PuFFInS)T32HL144470 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Carol A. Feghali-Bostwick · 2019 to 2026
$2.6M
IGF-II regulates lung fibrosis in sclerodermaR01HL153195 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI FEGHALI-BOSTWICK, CAROL A. · 2020 to 2023
$1.5M
Scleroderma Twin Study and analysis of Estrogen in patients with dcSScK24AR060297 · NIAMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FEGHALI-BOSTWICK, CAROL A. · 2013 to 2025
$1.4M
NHLBI NIH HHS R01 HL153195NHLBI NIH HHS T32 HL144470NHLBI NIH HHS T32HL144470NIAMS NIH HHS K24 AR060297
6 · The paper itself

Abstract

objectivesSystemic sclerosis (SSc) has the highest mortality rate among the rheumatic diseases, with lung fibrosis leading as the cause of death. A characteristic of severe SSc-related lung fibrosis is its progressive nature. Although most research has focused on the pathology of the fibrosis, the mechanism mediating the fibrotic spread remains unclear. We hypothesized that extracellular vesicle (EV) communication drives the propagation of SSc lung fibrosis.

methodsEVs were isolated from normal (NL) or SSc-derived human lungs and primary lung fibroblasts (pLFs). EVs were also isolated from human fibrotic lungs and pLFs induced experimentally with transforming growth factor-β (TGFβ). Fibrotic potency of EVs was assessed using functional assays in vitro and in vivo. Transmission electron microscopy, nanoparticle tracking analysis, real-time quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and immunofluorescence were used to analyze EVs, their cargo, extracellular matrix (ECM) fractions, and conditioned media.

resultsSSc lungs and pLFs released significantly more EVs than NL lungs, and their EVs showed increased fibrotic content and activity. TGFβ-stimulated NL lung cores and pLFs increased packaging of fibrotic proteins, including fibronectin, collagens, and TGFβ, into released EVs. The EVs induced a fibrotic phenotype in recipient pLFs and in vivo in mouse lungs. Furthermore, EVs interacted with and contributed to the ECM. Finally, suppressing EV release in vivo reduced severity of murine lung fibrosis.

conclusionsOur findings highlight EV communication as a novel mechanism for propagation of SSc lung fibrosis. Identifying therapies that reduce EV release, activity, and/or fibrotic cargo in SSc patient lungs may be a viable therapeutic strategy to improve fibrosis.

Indexed as

Extracellular VesiclesPulmonary FibrosisScleroderma, SystemicAnimalsFibroblastsFibrosisHumansLungMiceSignal TransductionTransforming Growth Factor betaTransforming Growth Factor beta

Identifiers

PMID37390364
PMCPMC10756928
OpenAlexW4382653934

What OpenQuestion holds

Textmetadata
LicenceTDM
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.