Evidence map›Paper›PMID 35363522›Full record

ArticleScience advances2022

Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis.

Takafumi Kato, Giorgia Radicioni, Micah J Papanikolas, Georgi V Stoychev, Matthew R Markovetz, Kazuhiro Aoki, Melody Porterfield, Kenichi Okuda, Selene M Barbosa Cardenas, Rodney C Gilmore and 20 more

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

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. Structural and cellular mechanisms of mucus plugging in the larger airways.Chinese medical journal pulmonary and critical care medicine · 2026
    Review
  4. Airway mucus in infection.Frontiers in physiology · 2026
    Review
  5. Article
  6. Article
  7. Cystic fibrosis.Nature reviews. Disease primers · 2024
    Review
  8. Article
  9. Review
  10. Towards a better mucolytic.The European respiratory journal · 2023
    Article
  11. Mucus aberrant properties in CF: Insights from cells and animal models.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2023
    Review
  12. Article
  13. Review
  14. Review
  15. Mucins and CFTR: Their Close Relationship.International journal of molecular sciences · 2022
    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

30 authors at 5 institutions in 2 countries.

Takafumi KatoMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0003-2248-3376
Giorgia RadicioniMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-5016-5426
Micah J PapanikolasDepartment of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0003-2691-5113
Georgi V StoychevMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-6824-3568
Matthew R MarkovetzMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0003-3931-0594
Kazuhiro AokiComplex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.ORCID 0000-0003-0029-4291
Melody PorterfieldComplex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.ORCID 0000-0001-6218-7366
Kenichi OkudaMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-9341-2730
Selene M Barbosa CardenasMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0003-2558-4893
Rodney C GilmoreMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-3821-8422
Cameron B MorrisonMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-4031-9521
Camille EhreMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-0046-0096
Kimberlie A BurnsMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kristen K WhiteDepartment of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-9882-8679
Tara A BrennanMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Henry P GoodellMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Holly ThackerMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Henry T LoznevMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lawrence J ForsbergProtein Expression and Purification Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-4787-9847
Takahide NagaseDepartment of Respiratory Medicine, University of Tokyo, Tokyo, Japan.
Michael RubinsteinDepartment of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA.ORCID 0000-0002-5455-0951
Scott H RandellMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-5351-2841
Michael TiemeyerComplex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.ORCID 0000-0002-8704-9143
David B HillMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-9270-777X
Mehmet KesimerMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0003-3867-1873
Wanda K O'NealMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Stephen T BallardDepartment of Physiology and Cell Biology, University of South Alabama, Mobile, AL, USA.
Ronit FreemanDepartment of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-5960-6689
Brian ButtonMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0001-8623-0576
Richard C BoucherMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID 0000-0002-5745-3989
University of North Carolina at Chapel Hill · USUniversity of Georgia · USDuke University · USThe University of Tokyo · JPUniversity of South Alabama · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
Vector CoreP30DK065988 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Martina Gentzsch · 2004 to 2026
$26.5M
The Biophysics of Mucus Hydration and Adhesion/CohesionP01HL108808 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBINSTEIN, MICHAEL · 2012 to 2021
$23.9M
TR&D1: Stem Cell and Induced Pluripotent Stem Cell Resources (Pages 116-134)P41GM103490 · NIGMS · UNIVERSITY OF GEORGIA · PI PIERCE, J. MICHAEL · 2012 to 2018
$13.7M
Purinergic Control of CFTR-ENaC Interactions in Alveolar EpitheliaP01HL110873 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2012 to 2016
$10.7M
GlyGen Supplement: Develop automatic literature mining tool for extracting context specific glycan-protein data that will enhance the extent and quality of data in GlyGenU01GM125267 · NIGMS · UNIVERSITY OF GEORGIA · PI MAZUMDER, RAJA, TIEMEYER, MICHAEL · 2017 to 2021
$10.2M
Synthesis of Effective and Safe Mucolytics for Pulmonary DiseaseUH3HL123645 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2016 to 2018
$4.6M
Multiscale Biochemical/Biophysical Integration of Pulmonary Mucus TransportR01HL136961 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2017 to 2020
$3.2M
The role of mucus and pulmonary surface interactions in lung defenseR01HL125280 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUTTON, BRIAN M · 2015 to 2023
$3.1M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016086NHLBI NIH HHS P01 HL108808NHLBI NIH HHS P01 HL110873NHLBI NIH HHS R01 HL125280NHLBI NIH HHS R01 HL136961NHLBI NIH HHS UH3 HL123645NIDDK NIH HHS P30 DK065988NIGMS NIH HHS P41 GM103490NIGMS NIH HHS U01 GM125267
6 · The paper itself

Abstract

Cystic fibrosis (CF) is characterized by abnormal transepithelial ion transport. However, a description of CF lung disease pathophysiology unifying superficial epithelial and submucosal gland (SMG) dysfunctions has remained elusive. We hypothesized that biophysical abnormalities associated with CF mucus hyperconcentration provide a unifying mechanism. Studies of the anion secretion-inhibited pig airway model of CF revealed elevated SMG mucus concentrations, osmotic pressures, and SMG mucus accumulation. Human airway studies revealed hyperconcentrated CF SMG mucus with raised osmotic pressures and cohesive forces predicted to limit SMG mucus secretion/release. Using proline-rich protein 4 (PRR4) as a biomarker of SMG secretion, CF sputum proteomics analyses revealed markedly lower PRR4 levels compared to healthy and bronchiectasis controls, consistent with a failure of CF SMGs to secrete mucus onto airway surfaces. Raised mucus osmotic/cohesive forces, reflecting mucus hyperconcentration, provide a unifying mechanism that describes disease-initiating mucus accumulation on airway surfaces and in SMGs of the CF lung.

Indexed as

Cystic FibrosisAnimalsCystic Fibrosis Transmembrane Conductance RegulatorMucusRespiratory SystemSputumSwineCystic Fibrosis Transmembrane Conductance Regulator

Identifiers

PMID35363522
PMCPMC10938572
OpenAlexW4221123416

What OpenQuestion holds

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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.