Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture.

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with high morbidity and mortality. The cellular source of the fibrotic process is currently under debate with o...

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Bibliographic Details
Published in:Laboratory Investigation
Main Authors: Jonsdottir, Hulda R, Arason, Ari J, Palsson, Ragnar, Franzdottir, Sigridur R, Gudbjartsson, Tomas, Isaksson, Helgi J, Gudmundsson, Gunnar, Gudjonsson, Thorarinn, Magnusson, Magnus K
Other Authors: 1 Univ Iceland, Fac Med, Biomed Ctr, Stem Cell Res Unit, IS-101 Reykjavik, Iceland 2 Landspitali Univ Hosp, Dept Lab Hematol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 3 Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland 4 Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 5 Landspitali Univ Hosp, Dept Cardiothorac Surg, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 6 Landspitali Univ Hosp, Dept Resp Med & Sleep, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 7 Univ Iceland, Fac Med, Dept Pharmacol & Toxicol, IS-101 Reykjavik, Iceland
Format: Article in Journal/Newspaper
Language:English
Published: Nature Publishing Group 2015
Subjects:
Idiopathic Pulmonary Fibrosis
Epithelial Cells
Stem Cells
Intravital Microscopy
Lung Diseases
Gene Expression
Cell Differentiation
Neoplasms
Anchorage
Iceland
Online Access:http://hdl.handle.net/2336/592869
https://doi.org/10.1038/labinvest.2015.114
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Summary:To access publisher's full text version of this article click on the hyperlink at the bottom of the page Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with high morbidity and mortality. The cellular source of the fibrotic process is currently under debate with one suggested mechanism being epithelial-to-mesenchymal transition (EMT) in the alveolar region. In this study, we show that airway epithelium overlying fibroblastic foci in IPF contains a layer of p63-positive basal cells while lacking ciliated and goblet cells. This basal epithelium shows increased expression of CK14, Vimentin and N-cadherin while retaining E-cadherin. The underlying fibroblastic foci shows both E- and N-cadherin-positive cells. To determine if p63-positive basal cells were able to undergo EMT in culture, we treated VA10, a p63-positive basal cell line, with the serum replacement UltroserG. A sub-population of treated cells acquired a mesenchymal phenotype, including an E- to N-cadherin switch. After isolation, these cells portrayed a phenotype presenting major hallmarks of EMT (loss of epithelial markers, gain of mesenchymal markers, increased migration and anchorage-independent growth). This phenotypic switch was prevented in p63 knockdown (KD) cells. In conclusion, we show that airway epithelium overlying fibroblastic foci in IPF lacks its characteristic functional identity, shows increased reactivity of basal cells and acquisition of a partial EMT phenotype. This study suggests that some p63-positive basal cells are prone to phenotypic changes and could act as EMT progenitors in IPF. Icelandic Research Council project/120423021 University of Iceland Research- and Doctoral Studies Fund Landspitali University Hospital Scientific Fund

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