Proteomic Analysis of Naphthalene-Induced Airway Epithelial Injury and Repair in a Cystic Fibrosis Mouse Model

Department of Cell Biology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Journal of Proteome Research (Impact Factor: 4.25). 06/2009; 8(7):3606-16. DOI: 10.1021/pr900021m
Source: PubMed


Combined results from laser capture microdissection of mouse airway epithelial cells followed by high power (MALDI-FTICR) MS, and fluorescent two-dimensional gel elctrophoresis (2D-DIGE) of the whole lung, allowed us to identify proteins differentially expressed after naphthalene induced airway injury. Further, we discovered several novel aspects of Cystic Fibrosis (CF) lung pathology in an F508del-Cftr mouse model using this approach. The combined MALDI-FTICR-MS and 2D-DIGE data show that lung carbonyl reductase (CBR2), involved in prostaglandin metabolism, converting PGE2 to PGF2alpha, is localized to airway cells and is reduced 2-fold in mutant mice compared to normal, both before and after challenge. Further, we observe a downregulation of two key enzymes of retinoic acid metabolism after injury, which is more pronounced in CF mutant mice. These data show that state-of-the-art proteomics can be used to evaluate airway injury in small cell samples. Further, the results suggest the involvement of prostaglandin and retinoic acid metabolism in the abnormal responses of CF mutant mice to injury.

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    • "Global comparative analyses of CF versus non-CF samples have been used to identify differentially expressed proteins in human bronchoalveolar lavage fluid (BALF) [20,21], sputum [22], bronchial biopsy tissue [23], serum [24] and cultured epithelial cells [25,26], and in mouse lung and colonic tissue [27-29]. Many of the proteins highlighted by global analyses can be related functionally to biological processes and pathways known to contribute to CF disease pathogenesis, including chronic inflammation, proteolytic activity and oxidative stress response proteins. "
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