The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity.

Abstract

Mainstay therapeutics are ineffective in some people with asthma, suggesting a need for additional agents. In the current study, we used vagal ganglia transcriptome profiling and connectivity mapping to identify compounds beneficial for alleviating airway hyperreactivity (AHR). As a comparison, we also used previously published transcriptome data from sensitized mouse lungs and human asthmatic endobronchial biopsies. All transcriptomes revealed agents beneficial for mitigating AHR; however, only the vagal ganglia transcriptome identified agents used clinically to treat asthma (flunisolide, isoetarine). We also tested one compound identified by vagal ganglia transcriptome profiling that had not previously been linked to asthma and found that it had bronchodilator effects in both mouse and pig airways. These data suggest that transcriptome profiling of the vagal ganglia might be a novel strategy to identify potential asthma therapeutics.

• Authors: Leah R Reznikov, David K Meyerholz, Mahmoud Abou Alaiwa, Shin-Ping Kuan, Yan-Shin J Liao, Nicholas L Bormann, Thomas B Bair, Margaret Price, David A Stoltz, Michael J Welsh
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 315 Issue 2 Pg. L133-L148 (08 01 2018) ISSN: 1522-1504 [Electronic] United States
• PMID: 29631359 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Bronchial Hyperreactivity (genetics, metabolism, pathology, therapy)
• Ganglia, Parasympathetic (metabolism, pathology)
• Male
• Mice
• Mice, Knockout
• Transcriptome
• Vagus Nerve (metabolism, pathology)