Usage Information
Citation Information: JCI Insight. 2019;4(8):e125954. https://doi.org/10.1172/jci.insight.125954.
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 Ca2+ 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 Ca2+-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.
Authors
Courtney M. Fernandez-Petty, Gareth W. Hughes, Hannah L. Bowers, John D. Watson, Bradley H. Rosen, Stacy M. Townsend, Carlo Santos, Caroline E. Ridley, Kengyeh K. Chu, Susan E. Birket, Yao Li, Hui Min Leung, Marina Mazur, Bryan A. Garcia, T. Idil Apak Evans, Emily Falk Libby, Heather Hathorne, Justin Hanes, Guillermo J. Tearney, John P. Clancy, John F. Engelhardt, William E. Swords, David J. Thornton, William P. Wiesmann, Shenda M. Baker, Steven M. Rowe
Usage data is cumulative from March 2022 through March 2023.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,084 | 333 |
| 112 | 45 | |
| Figure | 151 | 9 |
| Supplemental data | 177 | 32 |
| Citation downloads | 36 | 0 |
| Totals | 1,560 | 419 |
| Total Views | 1,979 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
