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Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis.
Kato, Takafumi; Radicioni, Giorgia; Papanikolas, Micah J; Stoychev, Georgi V; Markovetz, Matthew R; Aoki, Kazuhiro; Porterfield, Melody; Okuda, Kenichi; Barbosa Cardenas, Selene M; Gilmore, Rodney C; Morrison, Cameron B; Ehre, Camille; Burns, Kimberlie A; White, Kristen K; Brennan, Tara A; Goodell, Henry P; Thacker, Holly; Loznev, Henry T; Forsberg, Lawrence J; Nagase, Takahide; Rubinstein, Michael; Randell, Scott H; Tiemeyer, Michael; Hill, David B; Kesimer, Mehmet; O'Neal, Wanda K; Ballard, Stephen T; Freeman, Ronit; Button, Brian; Boucher, Richard C.
Afiliación
  • Kato T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Radicioni G; Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan.
  • Papanikolas MJ; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Stoychev GV; Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Markovetz MR; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Aoki K; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Porterfield M; Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
  • Okuda K; Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
  • Barbosa Cardenas SM; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Gilmore RC; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Morrison CB; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Ehre C; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Burns KA; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • White KK; Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Brennan TA; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Goodell HP; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Thacker H; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Loznev HT; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Forsberg LJ; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Nagase T; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Rubinstein M; Protein Expression and Purification Core, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Randell SH; Department of Respiratory Medicine, University of Tokyo, Tokyo, Japan.
  • Tiemeyer M; Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA.
  • Hill DB; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Kesimer M; Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
  • O'Neal WK; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Ballard ST; Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Freeman R; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Button B; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Boucher RC; Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, USA.
Sci Adv ; 8(13): eabm9718, 2022 04.
Article en En | MEDLINE | ID: mdl-35363522
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fibrosis Quística Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fibrosis Quística Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos