I recently profiled gene expression in multiple mouse models of asthma and various other lung diseases. I analyzed lung gene expression in widely used models of allergic asthma, pulmonary infection, and lung fibrosis in several inbred mouse strains. From these studies, comparison of expression profiles from various allergen-driven models of asthma revealed a small set of """"""""asthma signature genes"""""""" which were significantly upregulated in most or all the asthma models but not in the other models. Included among these """"""""asthma signature"""""""" genes is murine NAD synthetase I (NADsynl). With our collaborators here at UCSF, we investigated the expression of human NADsynl in airway epithelial brush biopsy samples and found that it was significantly (p<0.005) increased in asthmatics compared with healthy subjects. NADsynl enhances production of NAD, in the process yielding L-glutamate, which is a precursor for arginine. Arginine is important for NO synthesis and for the generation of ornithine, urea, putrescine, and polyamines. Previous studies have linked these pathways to various aspects of asthma pathogenesis, including airway hyperreactivity, increased smooth muscle cell contraction, mucus production, and enhanced cell proliferation and collagen production. Therefore, we hypothesize that upregulation of NADsynl in the asthmatic lung contributes to asthma pathogenesis by promoting synthesis of arginine and key arginine metabolites. The proposed work will employ a set of complementary approaches to help us understand how NADsynl contributes to asthma pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI063806-04
Application #
7168426
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Prograis, Lawrence J
Project Start
2005-02-16
Project End
2008-02-15
Budget Start
2007-02-16
Budget End
2008-02-15
Support Year
4
Fiscal Year
2007
Total Cost
$52,048
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229