Senescence and autophagy in usual interstitial pneumonia of different etiology
- PDF / 1,552,974 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 98 Downloads / 230 Views
ORIGINAL ARTICLE
Senescence and autophagy in usual interstitial pneumonia of different etiology Florian Gallob 1 & Luka Brcic 1 & Sylvia Eidenhammer 1 & Florian Rumpp 2 & Andreas Nerlich 3 & Helmut Popper 1 Received: 5 April 2020 / Revised: 15 July 2020 / Accepted: 19 August 2020 # The Author(s) 2020
Abstract Idiopathic pulmonary fibrosis (IPF) is a disease with a dismal prognosis. Currently, the causing agent(s) are poorly understood. Recent data suggest that senescence and autophagy might play a role in its development, as well as changes in metabolism due to hypoxic conditions. In this study, the expression of senescence markers in 23 cases of usual interstitial pneumonia (UIP)/IPF and UIP/chronic autoimmune diseases (UIP/AuD) was investigated. The status of autophagy was evaluated with respect to either antiinflammatory or antihypoxia function. Formalin-fixed paraffin-embedded tissues of UIP were selected for immunohistochemistry with antibodies for p21, p16, and β-galactosidase (senescence); for LC3, SIRT1, MAP1S, and pAMKα (autophagy); and for LDH and GLUT1 (metabolism). Epithelial cells in cystic remodeled areas of UIP stained for p16 and p21, p16 being more specific compared with p21. Myofibroblasts were negative in all cases. An upregulation of all four autophagy markers was seen not only in epithelia within remodeled areas and proliferating myofibroblasts, but also in bronchial epithelia and pneumocytes. Upregulated autophagy points to a compensatory mechanism for hypoxia; therefore, LDH and GLUT1 were investigated. Their expression was present in epithelia within cystic remodeling and in myofibroblasts. The cells within the remodeled areas stained for cytokeratin 5, but coexpressed TTF1, confirming their origin from basal cells of bronchioles. Within this population, senescent cells arise. Our results indicated that autophagy in UIP very likely helps cells to survive in hypoxic condition. By phagocytosis of cellular debris, they supplement their need for nutrition, and by upregulating LDH and GLUT1, they compensate for local hypoxia. Keywords IPF . UIP . Senescence . p16 TTF1 . Myofibroblast . Hypoxia . LDH
. Autophagy . LC3 . SIRT . MAP1S . pAMKα . Regeneration in cysts . Cytokeratin 5 . . GLUT1
Introduction Interstitial lung diseases (ILDs) are a heterogenous group of diseases with different etiology, clinical, radiological, and histologic presentation. They can be classified based on etiology (known and unknown) or based on histology, with usual interstitial pneumonia (UIP) as the most common pattern [24,
Master thesis work of Florian Gallob * Helmut Popper [email protected] 1
Diagnostic and Research Institute of Pathology, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010 Graz, Austria
2
Pulmonology Department, Clinics Munich-Bogenhausen, Munich, Germany
3
Pathology Department, Clinics Munich-Bogenhausen, Munich, Germany
44, 49, 60]. Idiopathic pulmonary fibrosis (IPF) is the most severe disease characterized by an UIP pattern. Many aspects of the pathogenesis have been
Data Loading...
