Journal article
A glycopolymer improves vascoelasticity and mucociliary transport of abnormal cystic fibrosis mucus
JCI insight, Vol.4(8), e125954
04/18/2019
DOI: 10.1172/jci.insight.125954
PMCID: PMC6538343
PMID: 30996141
Abstract
Cystic fibrosis (CF) is characterized by increased mucus viscosity and delayed mucociliary clearance that contributes to progressive decline of lung function. Mucus in the respiratory and GI tract is excessively adhesive in the presence of airway dehydration and excess extracellular Ca
2+
upon mucin release, promoting hyperviscous, densely packed mucins characteristic of CF. Therapies that target mucins directly through ionic interactions remain unexploited. Here we show that poly (acetyl, arginyl) glucosamine (PAAG), a polycationic biopolymer suitable for human use, interacts directly with mucins in a Ca
2+
-sensitive manner to reduce CF mucus viscoelasticity and improve its transport. Notably, PAAG induced a linear structure of purified MUC5B and altered its sedimentation profile and viscosity, indicative of proper mucin expansion. In vivo, PAAG nebulization improved mucociliary transport in CF rats with delayed mucus clearance, and cleared mucus plugging in CF ferrets. This study demonstrates the potential use of a synthetic glycopolymer PAAG as a molecular agent that could benefit patients with a broad array of mucus diseases.
The biopolymer poly (acetyl, arginyl) glucosamine improves abnormal viscoelastic properties of cystic fibrosis mucus, a major contributor to cystic fibrosis pathogenesis.
Details
- Title: Subtitle
- A glycopolymer improves vascoelasticity and mucociliary transport of abnormal cystic fibrosis mucus
- Creators
- Courtney M Fernandez-Petty - Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USAGareth W Hughes - Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, United KingdomHannah L Bowers - Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USAJohn D Watson - Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USABradley H Rosen - Department of Anatomy & Cell Biology andStacy M Townsend - Synedgen Inc., Claremont, California, USACarlo Santos - Synedgen Inc., Claremont, California, USACaroline E Ridley - Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, United KingdomKengyeh K Chu - Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USASusan E Birket - Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USAYao Li - Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USAHui Min Leung - Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USAMarina Mazur - Gregory Fleming James Cystic Fibrosis Research Center, andBryan A Garcia - Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USAT. Idil Apak Evans - Department of Anatomy & Cell Biology andEmily Falk Libby - Gregory Fleming James Cystic Fibrosis Research Center, andHeather Hathorne - Gregory Fleming James Cystic Fibrosis Research Center, andJustin Hanes - Center for Nanomedicine and Departments of Biomedical Engineering, Chemical & Biomolecular Engineering, Environmental Health Sciences, Neurosurgery, Oncology, Ophthalmology, and Pharmacology & Molecular Sciences, Johns Hopkins University, Baltimore, Maryland, USAGuillermo J Tearney - Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USAJohn P Clancy - Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USAJohn F Engelhardt - Department of Anatomy & Cell Biology andWilliam E Swords - Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USADavid J Thornton - Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, United KingdomWilliam P Wiesmann - Synedgen Inc., Claremont, California, USAShenda M Baker - Synedgen Inc., Claremont, California, USASteven M Rowe - Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.4(8), e125954
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/jci.insight.125954
- PMID
- 30996141
- PMCID
- PMC6538343
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Grant note
- R01HL1116213,R43HL118867,R01HL125169,P30 DK072482,R24 HL123482,P30 DK054759 / National Institute of Health (NIH) 088785/Z/09/Z / ; ROWE10XX0,THORNT07XXX0,HANES07XX0,HANES16XX0,ROSEN17XX0,R464-CF11 / ;
- Language
- English
- Date published
- 04/18/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025311502771
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