Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: The role of ΔN-p63

Marco Chilosi, Venerino Poletti, Bruno Murer, Maurizio Lestani, Alessandra Cancellieri, Licia Montagna, Paola Piccoli, Giulia Cangi, Gianpietro Semenzato, Claudio Doglioni

Research output: Contribution to journalArticle

Abstract

Products of the p63 gene, a recently described member of the p53 family, are constitutively expressed in the basal cells of human bronchi and bronchioli. The truncated isoforms of the p63 gene (ΔN-p63 proteins) counteract the apoptotic and cell cycle inhibitory functions of p53 after DNA damage, and this property is likely to be central in the cell renewal strategy of stratified epithelial tissues. To investigate the dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we immunohistochemically analyzed the expression of the transactivating and dominant-negative isoforms of the p63 gene on 16 tissue samples obtained from patients suffering from this disorder. In most IPF cases herein investigated, epithelial cells expressing ΔN-p63 were observed at sites of abnormal proliferation at the bronchiolo-alveolar junctions, characterized by epithelial hyperplasia, squamous metaplasia, bronchiolization, and abnormal p53 nuclear accumulation. Similar features were not observed in normal lung and in samples taken from other pulmonary diseases used as controls, including acute interstitial pneumonia, idiopathic bronchiolitis obliterans organizing pneumonia, nonspecific interstitial pneumonia, and desquamative interstitial pneumonia. On the basis of these findings, we can hypothesize a new model for UIP pathogenesis, involving a deregulated development of mesenchymal-epithelial interactions and abnormal proliferation of epithelial cells at the bronchiolo-alveolar junction after cell injury. In our view, the progressive loss of alveolar tissue and lung remodeling after injury in IPF/UIP is concomitantly produced by pneumocyte loss and alveolar collapse on one hand and by progressive bronchiolar proliferation and architectural distortion on the other.

Original languageEnglish
Pages (from-to)1335-1345
Number of pages11
JournalLaboratory Investigation
Volume82
Issue number10
Publication statusPublished - Oct 2002

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Re-Epithelialization
Idiopathic Pulmonary Fibrosis
Lung
Interstitial Lung Diseases
Protein Isoforms
Epithelial Cells
Idiopathic Interstitial Pneumonias
Cryptogenic Organizing Pneumonia
Genes
Alveolar Epithelial Cells
Intercellular Junctions
Wounds and Injuries
Metaplasia
Bronchi
Lung Diseases
DNA Damage
Hyperplasia
Cell Cycle
Epithelium
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Chilosi, M., Poletti, V., Murer, B., Lestani, M., Cancellieri, A., Montagna, L., ... Doglioni, C. (2002). Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: The role of ΔN-p63. Laboratory Investigation, 82(10), 1335-1345.

Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis : The role of ΔN-p63. / Chilosi, Marco; Poletti, Venerino; Murer, Bruno; Lestani, Maurizio; Cancellieri, Alessandra; Montagna, Licia; Piccoli, Paola; Cangi, Giulia; Semenzato, Gianpietro; Doglioni, Claudio.

In: Laboratory Investigation, Vol. 82, No. 10, 10.2002, p. 1335-1345.

Research output: Contribution to journalArticle

Chilosi, M, Poletti, V, Murer, B, Lestani, M, Cancellieri, A, Montagna, L, Piccoli, P, Cangi, G, Semenzato, G & Doglioni, C 2002, 'Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: The role of ΔN-p63', Laboratory Investigation, vol. 82, no. 10, pp. 1335-1345.
Chilosi M, Poletti V, Murer B, Lestani M, Cancellieri A, Montagna L et al. Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: The role of ΔN-p63. Laboratory Investigation. 2002 Oct;82(10):1335-1345.
Chilosi, Marco ; Poletti, Venerino ; Murer, Bruno ; Lestani, Maurizio ; Cancellieri, Alessandra ; Montagna, Licia ; Piccoli, Paola ; Cangi, Giulia ; Semenzato, Gianpietro ; Doglioni, Claudio. / Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis : The role of ΔN-p63. In: Laboratory Investigation. 2002 ; Vol. 82, No. 10. pp. 1335-1345.
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AU - Cancellieri, Alessandra

AU - Montagna, Licia

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