Aberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis

To investigate the molecular events that may underpin dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we analyzed the expression patterns of β-catenin on 20 IPF/UIP lung samples, together with two downstream target genes of Wnt s...

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Veröffentlicht in:The American journal of pathology 2003-05, Vol.162 (5), p.1495-1502
Hauptverfasser: Chilosi, Marco, Poletti, Venerino, Zamò, Alberto, Lestani, Maurizio, Montagna, Licia, Piccoli, Paola, Pedron, Serena, Bertaso, Manuela, Scarpa, Aldo, Murer, Bruno, Cancellieri, Alessandra, Maestro, Roberta, Semenzato, Gianpietro, Doglioni, Claudio
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container_issue 5
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container_title The American journal of pathology
container_volume 162
creator Chilosi, Marco
Poletti, Venerino
Zamò, Alberto
Lestani, Maurizio
Montagna, Licia
Piccoli, Paola
Pedron, Serena
Bertaso, Manuela
Scarpa, Aldo
Murer, Bruno
Cancellieri, Alessandra
Maestro, Roberta
Semenzato, Gianpietro
Doglioni, Claudio
description To investigate the molecular events that may underpin dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we analyzed the expression patterns of β-catenin on 20 IPF/UIP lung samples, together with two downstream target genes of Wnt signaling, cyclin-D1, and matrilysin. In 18 of 20 cases of IPF/UIP investigated on serial sections, nuclear β-catenin immunoreactivity and abnormal levels of cyclin-D1 and matrilysin were demonstrated in proliferative bronchiolar lesions (basal-cell hyperplasia, squamous metaplasia, bronchiolization, honeycombing). The nature of these lesions was precisely defined using specific markers (ΔN-p63, surfactant-protein-A, cytokeratin-5). Interestingly, nuclear β-catenin accumulation was also demonstrated in fibroblast foci in most (16 of 20) IPF/UIP samples, often associated with bronchiolar lesions. Similar features were not observed in normal lung and other fibrosing pulmonary diseases (diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, desquamative interstitial pneumonia). Sequence analysis performed on DNA extracted from three samples of IPF/UIP did not reveal abnormalities affecting the β-catenin gene. On the basis of these findings new models for IPF/UIP pathogenesis can be hypothesized, centered on the aberrant activation of Wnt/β-catenin signaling, with eventual triggering of divergent epithelial regeneration at bronchiolo-alveolar junctions and epithelial-mesenchymal-transitions, leading to severe and irreversible remodeling of the pulmonary tissue.
doi_str_mv 10.1016/S0002-9440(10)64282-4
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subjects Adult
beta Catenin
Biological and medical sciences
Cytoskeletal Proteins - genetics
Fetus
Gene Expression Regulation
Humans
Lung - embryology
Medical sciences
Pneumology
Proto-Oncogene Proteins - genetics
Pulmonary Fibrosis - genetics
Pulmonary Fibrosis - pathology
Regular
Respiratory system : syndromes and miscellaneous diseases
Trans-Activators - genetics
Wnt Proteins
Zebrafish Proteins
title Aberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis
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