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Identifier

000387741

Title

Η έκφραση των υποδοχέων του επιδερμικού αυξητικού παράγοντα στους καπνιστές με η χωρίς χρόνια αποφρακτική πνευμονοπάθεια

Alternative Title

Expression of EGF receptors in smokers with and with out chronic obstructive pulmonary disease

Author

Αναγνώστης, Αριστοτέλης Β

Thesis advisor

Σιαφάκας, Νικόλαος

Reviewer

Σουρβίνος, Γεώργιος
Αντωνίου, Αικατερίνη
Παπαδάκη, Ελένη
Σαμώνης, Γεώργιος
Κουρούμαλης, Ηλίας
Κουτσόπουλος, Αναστάσιος

Abstract

Background Chronic obstructive pulmonary disease (COPD) is becoming a serious health problem in the West, with an alarming increase in new cases and deaths each year. In over 95% of patients with COPD, prolonged exposure to cigarette smoke is the primary, and usually only, environmental aetiological factor for developing this disease. Cigarette smoke contains more than 4000 chemical compounds, a large number of solid particles and several free radicals that lead to oxidative stress of lung epithelium. Under normal conditions, lung epithelium is the first line of immune defence against smoking. In COPD, this natural barrier is compromised, leading to abnormal epithelial remodeling and mucociliary system dysfunction. Growth factors receptors, such as the EGFR family, play a key role in this process. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ErbB) family activation. This study’s objective was to evaluate the expression of ErbB1–4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD). Materials and methods ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls. Results Microarray data analysis revealed that ErbB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1.62- to 2.45-fold, (P < 0.01). Real-time qPCR verified that patients with COPD had higher ErbB1–3 expression levels compared with non-COPD smokers (PErbB1< 0.001; PErbB2 = 0.003; PErbB3 = 0.003) and nonsmokers (PErbB1 = 0.019; PErbB2 = 0.005; PErbB3 = 0.011). On the other hand, ErbB4 mRNA levels gradually increased from nonsmokers (0.74 ± 0.19) to non-COPD smokers (1.11 ± 005) to patients with 14 COPD (1.57 ± 0.28) and were correlated with the degree of airflow obstruction (PFEV1 < 0.001). Discussion In this study, we observed an increased expression of ErbB receptors in patients with COPD, when compared to healthy smokers and controls. These data suggest that ErbB1–3 overexpression is not related only to smoking exposure but probably to epithelial remodelling and mucociliary system distortion, characterizing COPD. Additionally, the inverse correlation of ErbB4 with FEV1 exhibits a possible link between ErbB4 and COPD severity.

Language

English

Subject

Growth factors

Αυξητικοί παράγοντες

Υπέκριση βλέννης

Issue date

2014-07-24

Collection

School/Department--School of Medicine--Department of Medicine--Doctoral theses

Type of Work--Doctoral theses

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