Disulfide disruption reverses mucus dysfunction in allergic airway disease
| Autor: | Siddharth K. Shenoy, Corinne E. Hennessy, William J. Janssen, Fernando Holguin, Jung Soo Suk, Chelsea M. Magin, Christopher M. Evans, Ana M. Jaramillo, Vanessa L. Richardson, Naoko Hara, James C. NeeDell, Leslie E. Morgan, Diane E. Grove Villalon, Dorota S Raclawska, David J. Thornton, William R. Thelin, Nkechinyere A. Emezienna, Anna Q. Harder, Justin Hanes, Hassan M. El-Batal, Gregg A. Duncan |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male General Physics and Astronomy urologic and male genital diseases Biochemistry Mice 0302 clinical medicine fluids and secretions immune system diseases Bronchodilator Medicine 030212 general & internal medicine Disulfides Respiratory system Lung Expectorants 0303 health sciences Mice Inbred BALB C Multidisciplinary Middle Aged respiratory system 3. Good health medicine.anatomical_structure Female medicine.symptom medicine.drug Adult Adolescent medicine.drug_class Mucociliary clearance Science Inflammation General Biochemistry Genetics and Molecular Biology Article Allergic inflammation 03 medical and health sciences In vivo Hypersensitivity Animals Humans 030304 developmental biology Asthma Glycoproteins business.industry Mucin General Chemistry Translational research medicine.disease Mucus respiratory tract diseases Disease Models Animal 030104 developmental biology 030228 respiratory system Immunology Methacholine business |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-9 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Airway mucus is essential for lung defense, but excessive mucus in asthma obstructs airflow, leading to severe and potentially fatal outcomes. Current asthma treatments have minimal effects on mucus, and the lack of therapeutic options stems from a poor understanding of mucus function and dysfunction at a molecular level and in vivo. Biophysical properties of mucus are controlled by mucin glycoproteins that polymerize covalently via disulfide bonds. Once secreted, mucin glycopolymers can aggregate, form plugs, and block airflow. Here we show that reducing mucin disulfide bonds disrupts mucus in human asthmatics and reverses pathological effects of mucus hypersecretion in a mouse allergic asthma model. In mice, inhaled mucolytic treatment loosens mucus mesh, enhances mucociliary clearance, and abolishes airway hyperreactivity (AHR) to the bronchoprovocative agent methacholine. AHR reversal is directly related to reduced mucus plugging. These findings establish grounds for developing treatments to inhibit effects of mucus hypersecretion in asthma. In asthma, mucus plugging is an important cause of airflow obstruction, but it is not targeted by widely used bronchodilator and anti-inflammatory drugs. Here the authors show that reduction of disulfide bonds that hold mucin polymers together reverses asthma-like obstruction in mice. |
| Databáze: | OpenAIRE |
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