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ORIGINAL ARTICLE
Telomerase in pulmonary fibrosis: A link to alveolar cell apoptosis and differentiation
1
Department of Pneumonology, University Hospital of Alexandroupolis, Medical school, Democritus University of Thrace, Greece
2
Department of Pathology, VA Hospital - N.I.M.T.S, Athens, Greece
3
Department of Pathology, University Hospital of Heraklion, Crete
4
Department of Pathology, Sotiria General Hospital, Athens, Greece
5
Department of Cardiothoracic surgery, University Hospital of Alexandroupolis, Medical school, Democritus University of Thrace, Greece
6
Department of Hematology, University Hospital of Alexandroupolis, Medical school, Democritus University of Thrace, Greece
Corresponding author
Argyris Tzouvelekis
Medical School, Democritus University of Thrace, Department of Pneumonology, University Hospital of Alexandroupolis, Alexandroupolis 68100
Medical School, Democritus University of Thrace, Department of Pneumonology, University Hospital of Alexandroupolis, Alexandroupolis 68100
Pneumon 2010;23(3):224-239
KEYWORDS
ABSTRACT
Introduction:
Telomerase is crucial for extended life span and differentiation and is linked to immortality. Therefore, its role may be crucial in the pathogenesis of pulmonary fibrosis. Our objective was to implicate telomerase in the pathogenesis of idiopathic fibrotic lung disease.
Patients and Methods:
Assessment of telomerase activity and expression was carried out using TRAP detection kit and qRT-PCR. Experimental procedure was enhanced by a series of immunostainings and fluorescence in situ hybridization analysis in tissue microarrays constructed with tissue samples from patients with idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP).
Results:
We demonstrated significant downregulation of telomerase expression and activity in patients with fibrotic lung disease compared to controls. Immunolocalization studies coupled by FISH analysis revealed the presence of two subpopulations of type II AECs based on their telomerase expression levels: telomerase positive type II AECs, mainly overlying areas of active fibrosis and telomerase negative type II AECs, mainly localized in areas of established fibrosis.
Conclusions:
Downregulation of telomerase expression and activity in IPF may indicate a causal relationship between low telomerase expression and disease pathogenesis. The duality phenomenon in telomerase expression suggests that telomerase may regulate the fate of AECs towards either an apoptotic or a mesenchymal phenotype contributing directly to fibrosis.
Telomerase is crucial for extended life span and differentiation and is linked to immortality. Therefore, its role may be crucial in the pathogenesis of pulmonary fibrosis. Our objective was to implicate telomerase in the pathogenesis of idiopathic fibrotic lung disease.
Patients and Methods:
Assessment of telomerase activity and expression was carried out using TRAP detection kit and qRT-PCR. Experimental procedure was enhanced by a series of immunostainings and fluorescence in situ hybridization analysis in tissue microarrays constructed with tissue samples from patients with idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP).
Results:
We demonstrated significant downregulation of telomerase expression and activity in patients with fibrotic lung disease compared to controls. Immunolocalization studies coupled by FISH analysis revealed the presence of two subpopulations of type II AECs based on their telomerase expression levels: telomerase positive type II AECs, mainly overlying areas of active fibrosis and telomerase negative type II AECs, mainly localized in areas of established fibrosis.
Conclusions:
Downregulation of telomerase expression and activity in IPF may indicate a causal relationship between low telomerase expression and disease pathogenesis. The duality phenomenon in telomerase expression suggests that telomerase may regulate the fate of AECs towards either an apoptotic or a mesenchymal phenotype contributing directly to fibrosis.
ACKNOWLEDGEMENTS
This work was partly supported by the Society for
Respiratory Research and Treatment of Eastern Macedonia
and Thrace (AT, DB) and a European Commission Network
of Excellence grant QLRT-CT-2001-01407 (V.A.) and a Hellenic Ministry for Development grant GSRTPENED- 136
(V.A.). AT is a recipient of an annual research grant in
respiratory medicine provided by GlaxoSmithKline for
the year 2005-2006. We are also grateful to Vassileios
Vasdekis (Department of Economics and Business, Kapodistrian University of Athens, Greece) for carrying out
the statistical analysis of our manuscript.
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