Evidence map›Paper›PMID 25717100›Full record

ArticleScience translational medicine2015

Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

Shaopeng Yuan, Martin Hollinger, Marrah E Lachowicz-Scroggins, Sheena C Kerr, Eleanor M Dunican, Brian M Daniel, Sudakshina Ghosh, Serpel C Erzurum, Belinda Willard, Stanley L Hazen and 4 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
15.1field-weighted citation impact, top 1% 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

134 citing papers in PubMed, 258 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Mucus Plugs and Eosinophilic Inflammation: Expanding the Paradigm to COPD.The journal of allergy and clinical immunology. In practice · 2026
    Review
  10. Article
  11. Airway mucus in infection.Frontiers in physiology · 2026
    Review
  12. Article
  13. Article
  14. Myeloperoxidase impairs mucociliary transport on human airway epithelium.bioRxiv : the preprint server for biology · 2025
    Article
  15. Article
  16. Hyperconcentrated mucus in small airways: a mechanistic model for the pathogenesis of paediatric bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  17. Article
  18. iScience · 2025
    Article
  19. Article
  20. Article

74 more citing papers are in PubMed but not listed here.

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

14 authors at 4 institutions in 2 countries.

Shaopeng YuanCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Martin HollingerCentre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin, Ireland.
Marrah E Lachowicz-ScrogginsDivision of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Sheena C KerrDivision of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Eleanor M DunicanDivision of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Brian M DanielDepartment of Respiratory Therapy, University of California, San Francisco, San Francisco, CA 94143, USA.
Sudakshina GhoshDepartment of Pathobiology, Proteomics Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Serpel C ErzurumDepartment of Pathobiology, Proteomics Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Belinda WillardDepartment of Pathobiology, Proteomics Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Stanley L HazenDepartment of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Xiaozhu HuangLung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Stephen D CarringtonVeterinary Science Center, University College Dublin, Dublin, Ireland.
Stefan OscarsonCentre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin, Ireland.
John V FahyCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA. Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. john.fahy@ucsf.edu.
University of California System · USCleveland Clinic · USUniversity College Dublin · IEUniversity of California, San Francisco · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Targeting pathological hyaluronan matricesP01HL103453 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI REIZES, OFER · 2011 to 2020
$26.8M
Role of miRNAs in Th2-Driven inflammation in AsthmaP01HL107202 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANSEL, KARL MARK · 2012 to 2023
$23.3M
SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Tissue Processing and Cell Culture COreP01HL081064 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI ARONICA, MARK A · 2006 to 2019
$17.8M
Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
Protein carbohydrate interactions in the pathophysiology of asthma exacerbationsR01HL080414 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI John V Fahy · 2005 to 2026
$9.2M
Airway redox biochemistry as a deteriminant of asthma phenotype during adolescen*U10HL109250 · NHLBI · UNIVERSITY OF VIRGINIA · PI ERZURUM, SERPIL C., GASTON, BENJAMIN · 2011 to 2016
$4.2M
Clinical and Molecular Phenotypes of Severe AsthmaU10HL109146 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAHY, JOHN V · 2011 to 2016
$4.0M
Preventing fucose-dependent binding of aspergillus and pseudomonas to lung mucinP50HL107191 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAHY, JOHN V · 2011 to 2012
$848k
NCATS NIH HHS UL1 TR000439NHLBI NIH HHS P01 HL081064NHLBI NIH HHS P01 HL103453NHLBI NIH HHS P01HL103453NHLBI NIH HHS P01 HL107202NHLBI NIH HHS P50 HL107191NHLBI NIH HHS P50HL107191NHLBI NIH HHS R01 HL080414NHLBI NIH HHS R01HL080414NHLBI NIH HHS R24 HL123767NHLBI NIH HHS U10 HL109146NHLBI NIH HHS U10 HL109250NIDDK NIH HHS P30 DK072517
6 · The paper itself

Abstract

Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates.

Indexed as

AcetylcysteineAnimalsBiomechanical PhenomenaCross-Linking ReagentsCystic FibrosisDisulfidesDNAElasticityExpectorantsGalactoseGelsHumansLungMice, Inbred C57BLMucinsMucusAcetylcysteineCross-Linking ReagentsDisulfidesDNAExpectorantsGalactoseGelsMucinsPolymersReducing AgentsSulfhydryl Compounds

Identifiers

PMID25717100
PMCPMC4403633
OpenAlexW2124843402

What OpenQuestion 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 OpenQuestion graph.