Post-graduate theses
Current Record: 713 of 1241
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| Identifier |
000395598 |
| Title |
Macrophage homeostasis in idiopathic pulmonary fibrosis (IPF) : a bronchoalveolar lavage fluid study |
| Alternative Title |
Ομοιόσταση των μακροφάγων στην ιδιοπαθή πνευμονική ίνωση(ΙΠΙ) |
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Author
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Βασαρμίδη, Ειρήνη
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Thesis advisor
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Αντωνίου, Κατερίνα
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Reviewer
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Σουρβίνος, Γεώργιος
Τσατσάνης, Χρήστος
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| Abstract |
Idiopathic Pulmonary Fibrosis (IPF) is a chronic and irreversible interstitial lung disease with poor prognosis and limited therapeutic options. The last decade much research has been done to reveal the pathogenetic mechanisms involved in this enigmatic lung disease. Autophagy is a process for the turnover of subcellular components and organelles and represents a major cellular homeostatic mechanism. The significance of mitochondria and their main role in energy regulation are well known. However, upon oxidative stress, mitochondria become dysmorphic and dysfunctional and need to be removed via selective autophagy, called mitophagy. Recent evidence suggests a role of autophagy and mitochondrial dysfunction in the development of IPF focusing on lung fibroblasts or epithelial cells. In this study, we focused on the evaluation of autophagy with an emphasis in mitophagy and oxidation status in macrophages from patients with IPF, using the Bronchoalveolar Lavage Fluid (BALF) derived cells in comparison with control subjects and patients with Rheumatoid Arthritis (RA) and lung involvement (ILD-interstitial lung disease). Our results indicated an increase in LC3 protein levels, accompanied by a decrease in p62 protein levels in IPF patients, with no difference in mRNA expression levels in genes involved in autophagy and mitophagy - such as Beclin1, ULK1, S100A9, p62, BNIP3, or AKT3- in IPF patients when compared to controls. Interestingly, we demonstrated a significant downregulation of PINK1 mRNA levels in IPF and RA-ILD patients versus controls. However, RA-ILD patients seem to display a distinct expression pattern with upregulation of Beclin1 and AKT3. Regarding the oxidation levels of mitochondria in IPF patients, we evaluated MitoSOX staining in fresh BALF cells from newly recruited patients. Our preliminary data showed a distinct population shift of the cells following flow cytometry analysis, indicating MitoSOX positivity in IPF patients, although the percentage of strongly MitoSOX positive cells was not statistically significant different when compared to controls. Finally, we assessed the effect of the master mediator in IPF pathogenesis, TGFβ1, in THP1 cells treated with PMA. We interestingly observed that TGFβ1 decreased MitoSOX levels as well as PINK1 expression.
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| Language |
English |
| Subject |
Autophagy |
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Mitochondria |
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Αυτοφαγία |
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Μιτοχονδρία |
| Issue date |
2015-07-17 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Permanent Link |
https://elocus.lib.uoc.gr//dlib/c/2/0/metadata-dlib-1441609969-906718-13311.tkl
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| Views |
337 |
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