Over 12 million Americans have chronic obstructive pulmonary disease (COPD). Although approximately 1 out of 5 cigarette smokers develop COPD, smoking accounts for 90% of development of COPD. We have evidence that the expression of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is suppressed in human samples from COPD patients and that cigarette smoke reduces the expression of CFTR in lung epithelial cells. CFTR is a chloride channel that is primarily expressed in epithelial cells where it regulates fluid homeostasis. Loss of CFTR function is associated with accumulation of mucus in the lung, abnormal inflammation and wound repair. Therefore, the potential importance of cigarette smoke-induced CFTR abnormalities in the pathophysiology of smoking-related diseases should be further evaluated. Over 10 million Americans are asymptomatic carriers of one CFTR mutation. This implicate that cigarette smoking will further decrease CFTR protein expression and might lead to increased risk of pulmonary diseases. This study will assess the contribution of CFTR to the development of COPD using a mouse model expressing reduced or no CFTR protein. This proposal will also identify the role of CFTR in lung responses to cigarette smoking. These studies will identify new markers that could be targeted for therapy.

Public Health Relevance

COPD is the fourth leading cause of death in the United States, with over 12 million Americans having this disease. This study will investigate the contribution of the CFTR protein involved in Cystic Fibrosis, in the development/worsening of COPD. This study will also identify new pathways that could be targeted to prevent the development of this disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL109969-02
Application #
8603277
Study Section
Lung Cellular, Molecular, and Immunobiology Study Section (LCMI)
Program Officer
Punturieri, Antonello
Project Start
2013-01-07
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
2
Fiscal Year
2014
Total Cost
$162,920
Indirect Cost
$50,420
Name
Ohio State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210