Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fabro, AT; Minatel, IO; Rangel, MP; Halbwedl, I; Parra, ER; Capelozzi, VL; Popper, H.
Usual interstitial pneumonia and smoking-related interstitial fibrosis display epithelial to mesenchymal transition in fibroblastic foci.
Respir Med. 2014; 108(9):1377-1386
Doi: 10.1016/j.rmed.2014.06.008
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- Co-Autor*innen der Med Uni Graz
- Halbwedl Iris
- Popper Helmuth
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- Abstract:
- Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (non-IPF). In addition, FF are occasionally associated with smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis. Here, we investigated whether EMT was present in patients with IPF (n = 19), non-IPF (n = 17), and SRIF (n = 16) using morphometric immunohistochemistry, electron microscopy, and confocal microscopy. All patients had received lung biopsies or lobectomies for lung cancer. IPF and non-IPF patients displayed restrictive lung function patterns, whereas those with SRIF presented mixed patterns. Cells within FF presented high number of alpha-smooth muscle actin (αSMA)-staining cells; however, the foci of IPF patients showed comparatively lower number. Moreover, colocalization of thyroid transcription factor-1 (TTF1) and αSMA within FF showed low number of staining cells for IPF and SRIF in comparison to non-IPF (p < 0.01). Nevertheless, all groups displayed colocalization of high rate of TTF1(+)-cells and low rate of αSMA(+)-cells within hyperplastic epithelioid cells in FF. Also, we observed areas with low proportion of TTF1(+)cells and αSMA(+)cells, which were present in SRIF and non-IPF more often than IPF (p < 0.001). Electron microscopy revealed small breaks in the alveolar basal lamina, which allowed epithelioid cells to directly contact the collagenous matrix and fibroblasts. Three-dimensional reconstruction revealed intense αSMA staining within some epithelioid cells, suggesting that they had gained a mesenchymal phenotype. These findings constitute the first report of EMT in SRIF and suggest that EMT occurs more prominently in SRIF and non-IPF than IPF. Copyright © 2014 Elsevier Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Epithelial-Mesenchymal Transition - physiology
- Female -
- Fibroblasts - pathology
- Fibroblasts - ultrastructure
- Humans -
- Imaging, Three-Dimensional - methods
- Lung Diseases, Interstitial - pathology
- Lung Diseases, Interstitial - physiopathology
- Male -
- Microscopy, Confocal -
- Microscopy, Electron -
- Middle Aged -
- Pulmonary Fibrosis - etiology
- Pulmonary Fibrosis - pathology
- Pulmonary Fibrosis - physiopathology
- Smoking - adverse effects
- Find related publications in this database (Keywords)
- Epithelial-mesenchymal transition
- Usual interstitial pneumonia
- Idiopathic pulmonary fibrosis
- Smoking-related interstitial fibrosis
- Double-staining immunohistochemistry