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Identification of New Molecular Pathways Involved in the Pathogenesis of Chronic Obstructive Pulmonary Disease by Proteomics Approaches

University of Pittsburgh, Pittsburgh, Pennsylvania; and St. Paul's Hospital–Providence Health Care, Vancouver, British Columbia, Canada

Correspondence and requests for reprints should be addressed to Augustine Choi, M.D., Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, MUH 628NW, 3459 5th Avenue, Pittsburgh, PA 15213. E-mail: choiam{at}upmc.edu

Comprehensive protein profiling is a powerful approach to identify new molecular pathways and targets to better understand the pathogenesis of chronic obstructive pulmonary disease (COPD). We applied proteomics approaches to identify differential protein profiling in human lung tissues (n = 3, GOLD [Global Initiative for Chronic Obstructive Lung Disease] 2 compared with GOLD 0; Group 1) and in primary cultured human lung fibroblasts (isolated from GOLD 2 and GOLD 0; Group 2) in response to cigarette smoke extracts (CSE; 20%, 8 h). Patient classification of GOLD 2 and GOLD 0 was carefully characterized. Each group was compared using two-dimensional difference gel electrophoresis. The two samples from each group were either labeled Cy3 or Cy5 and electrophoresed on the same gel to compare relative quantification of protein spots between both samples. Gel images were analyzed using DeCyder software (GE Health Care, Wankesha, WI), and the differentially expressed protein spots were manually excised for analysis. Proteins from each gel plug were digested by trypsin and analyzed with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry for protein identification. MALDI-TOF analysis demonstrated decreased levels of proteins such as Fibrin B and HSP27 and increased levels of keratin and ₁-antitrypsin in GOLD 2 human lungs compared with GOLD 0 control lungs. MALDI-TOF analysis identified decreases in proteins such as vimentin and zyxin in the fibroblast cultures from GOLD 2 human lung tissues after CSE treatment. In summary, we have demonstrated the feasibility of using proteomics approaches to identify potential new molecular targets using human lung tissues and cells from patients with COPD. The confirmation and biological validation of these proteins will provide a useful tool to unravel new molecular pathways in COPD.

FOOTNOTES

Conflict of Interest Statement: R.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.R.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.F.-B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.C.H. has served as a consultant, given lectures, and participated in advisory boards of several pharmaceutical companies in the past 3 years. The total reimbursement for these activities is less than $20,000. A.M.K.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form March 20, 2006; accepted in final form March 28, 2006)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Song, R. Articles by Choi, A. M. K. Search for Related Content PubMed Articles by Song, R. Articles by Choi, A. M. K.