Development and application of proteomics as aid for unraveling smoke-induced COPD

Franciosi, L., 2015, [Groningen]: University of Groningen. 128 p.

Research output: ThesisThesis fully internal (DIV)

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  • Lorenza Franciosi
The scope of this thesis was to identify potential biomarkers for Chronic Obstructive Pulmonary Disease (COPD) via a proteomic approach.
In order to identify the first processes involved in the onset of COPD, we aimed to compare not only confirmed (older) COPD patients with healthy controls, but also younger subjects susceptible or non-susceptible to develop the disease, based on their family history.
After assessing the feasibility of our proteomic approach in the investigation in Epithelial Lining Fluid (ELF), we firstly compared the differential proteomic profiles in COPD patients and healthy controls. The proteins that resulted as statistically significantly different between these groups were subsequently investigated via other approaches, namely immunohistochemistry and ELISA.
A comparative study of ELF from COPD patients and healthy controls using chemical stable isotope labeling (iTRAQ®-8Plex) showed that the levels of four proteins differed significantly between ELF from COPD patients and healthy controls. These proteins are directly involved in two of the key processes responsible for the onset and development COPD, namely inflammation and oxidative stress.
Cigarette smoking is the main risk factor for COPD, yet only a subset of smokers develops COPD, therefore in order to obtain a deeper understanding of the first processes responsible of the disease, we set up the acute smoking model in young susceptible and non-susceptible individuals, COPD patients and controls. Our data show that already at young age, subjects with a positive family history of COPD respond differently to cigarette smoke than those with a negative family history. Particularly SerpinB3 and Uteroglobin were found to be proteins that may play a role in the onset of COPD.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Award date27-Nov-2015
Place of Publication[Groningen]
Print ISBNs978-90-367-8245-6
Electronic ISBNs978-90-367-8244-9
Publication statusPublished - 2015

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