Skip to main content

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

Publication ,  Journal Article
Kato, T; Radicioni, G; Papanikolas, MJ; Stoychev, GV; Markovetz, MR; Aoki, K; Porterfield, M; Okuda, K; Barbosa Cardenas, SM; Gilmore, RC ...
Published in: Science advances
April 2022

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Science advances

DOI

EISSN

2375-2548

ISSN

2375-2548

Publication Date

April 2022

Volume

8

Issue

13

Start / End Page

eabm9718

Related Subject Headings

  • Swine
  • Sputum
  • Respiratory System
  • Mucus
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cystic Fibrosis
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kato, T., Radicioni, G., Papanikolas, M. J., Stoychev, G. V., Markovetz, M. R., Aoki, K., … Boucher, R. C. (2022). Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis. Science Advances, 8(13), eabm9718. https://doi.org/10.1126/sciadv.abm9718
Kato, Takafumi, Giorgia Radicioni, Micah J. Papanikolas, Georgi V. Stoychev, Matthew R. Markovetz, Kazuhiro Aoki, Melody Porterfield, et al. “Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis.Science Advances 8, no. 13 (April 2022): eabm9718. https://doi.org/10.1126/sciadv.abm9718.
Kato T, Radicioni G, Papanikolas MJ, Stoychev GV, Markovetz MR, Aoki K, et al. Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis. Science advances. 2022 Apr;8(13):eabm9718.
Kato, Takafumi, et al. “Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis.Science Advances, vol. 8, no. 13, Apr. 2022, p. eabm9718. Epmc, doi:10.1126/sciadv.abm9718.
Kato T, Radicioni G, Papanikolas MJ, Stoychev GV, Markovetz MR, Aoki K, Porterfield M, Okuda K, Barbosa Cardenas SM, Gilmore RC, Morrison CB, Ehre C, Burns KA, White KK, Brennan TA, Goodell HP, Thacker H, Loznev HT, Forsberg LJ, Nagase T, Rubinstein M, Randell SH, Tiemeyer M, Hill DB, Kesimer M, O’Neal WK, Ballard ST, Freeman R, Button B, Boucher RC. Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis. Science advances. 2022 Apr;8(13):eabm9718.

Published In

Science advances

DOI

EISSN

2375-2548

ISSN

2375-2548

Publication Date

April 2022

Volume

8

Issue

13

Start / End Page

eabm9718

Related Subject Headings

  • Swine
  • Sputum
  • Respiratory System
  • Mucus
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cystic Fibrosis
  • Animals