The vagal ganglia transcriptome identifies candidate therapeutics for airway hyperreactivity

Author:

Reznikov Leah R.1,Meyerholz David K.2ORCID,Abou Alaiwa Mahmoud34,Kuan Shin-Ping1,Liao Yan-Shin J.1,Bormann Nicholas L.3,Bair Thomas B.5,Price Margaret34,Stoltz David A.3647,Welsh Michael J.3648

Affiliation:

1. Department of Physiological Sciences, University of Florida, Gainesville, Florida

2. Department of Pathology, University of Iowa, Iowa City, Iowa

3. Department of Internal Medicine, University of Iowa, Iowa City, Iowa

4. Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa

5. Iowa Institute of Human Genetics, University of Iowa, Iowa City, Iowa

6. Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa

7. Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, Iowa

8. Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa

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.

Funder

NHLBI

NIH

American Asthma Foundation

Roy J Carver Charitable Trust

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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