دورية أكاديمية
Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness
| العنوان: | Antagonizing cholecystokinin A receptor in the lung attenuates obesity-induced airway hyperresponsiveness |
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| المؤلفون: | Panganiban, Ronald Allan M., Yang, Zhiping, Sun, Maoyun, Park, Chan Young, Kasahara, David I., Schaible, Niccole, Krishnan, Ramaswamy, Kho, Alvin T., Israel, Elliot, Hershenson, Marc B., Weiss, Scott T., Himes, Blanca E., Fredberg, Jeffrey J., Tantisira, Kelan G., Shore, Stephanie A., Lu, Quan |
| المساهمون: | American Asthma Foundation |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Obesity increases asthma prevalence and severity. However, the underlying mechanisms are poorly understood, and consequently, therapeutic options for asthma patients with obesity remain limited. Here we report that cholecystokinin—a metabolic hormone best known for its role in signaling satiation and fat metabolism—is increased in the lungs of obese mice and that pharmacological blockade of cholecystokinin A receptor signaling reduces obesity-associated airway hyperresponsiveness. Activation of cholecystokinin A receptor by the hormone induces contraction of airway smooth muscle cells. In vivo, cholecystokinin level is elevated in the lungs of both genetically and diet-induced obese mice. Importantly, intranasal administration of cholecystokinin A receptor antagonists (proglumide and devazepide) suppresses the airway hyperresponsiveness in the obese mice. Together, our results reveal an unexpected role for cholecystokinin in the lung and support the repurposing of cholecystokinin A receptor antagonists as a potential therapy for asthma patients with obesity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-022-35739-8 |
| الإتاحة: | https://doi.org/10.1038/s41467-022-35739-8Test https://www.nature.com/articles/s41467-022-35739-8.pdfTest https://www.nature.com/articles/s41467-022-35739-8Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.594D3DFF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-022-35739-8 |
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