PMID- 26390052
OWN - NLM
STAT- MEDLINE
DCOM- 20160318
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 95
IP  - 12
DP  - 2015 Dec
TI  - Basal cells of the human airways acquire mesenchymal traits in idiopathic 
      pulmonary fibrosis and in culture.
PG  - 1418-28
LID - 10.1038/labinvest.2015.114 [doi]
AB  - 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.
FAU - Jonsdottir, Hulda R
AU  - Jonsdottir HR
AD  - Stem Cell Research Unit, Biomedical Center, Faculty of Medicine, University of 
      Iceland, Reykjavik, Iceland.
AD  - Department of Laboratory Hematology, Landspitali University Hospital, Reykjavik, 
      Iceland.
AD  - Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
FAU - Arason, Ari J
AU  - Arason AJ
AD  - Stem Cell Research Unit, Biomedical Center, Faculty of Medicine, University of 
      Iceland, Reykjavik, Iceland.
AD  - Department of Laboratory Hematology, Landspitali University Hospital, Reykjavik, 
      Iceland.
AD  - Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
FAU - Palsson, Ragnar
AU  - Palsson R
AD  - Stem Cell Research Unit, Biomedical Center, Faculty of Medicine, University of 
      Iceland, Reykjavik, Iceland.
AD  - Department of Laboratory Hematology, Landspitali University Hospital, Reykjavik, 
      Iceland.
AD  - Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
FAU - Franzdottir, Sigridur R
AU  - Franzdottir SR
AD  - Stem Cell Research Unit, Biomedical Center, Faculty of Medicine, University of 
      Iceland, Reykjavik, Iceland.
AD  - Department of Laboratory Hematology, Landspitali University Hospital, Reykjavik, 
      Iceland.
FAU - Gudbjartsson, Tomas
AU  - Gudbjartsson T
AD  - Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
AD  - Department of Cardiothoracic Surgery, Landspitali University Hospital, Reykjavik, 
      Iceland.
FAU - Isaksson, Helgi J
AU  - Isaksson HJ
AD  - Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland.
FAU - Gudmundsson, Gunnar
AU  - Gudmundsson G
AD  - Department of Respiratory Medicine and Sleep, Landspitali University Hospital, 
      Reykjavik, Iceland.
AD  - Department of Pharmacology and Toxicology, Faculty of Medicine, University of 
      Iceland, Reykjavik, Iceland.
FAU - Gudjonsson, Thorarinn
AU  - Gudjonsson T
AD  - Stem Cell Research Unit, Biomedical Center, Faculty of Medicine, University of 
      Iceland, Reykjavik, Iceland.
AD  - Department of Laboratory Hematology, Landspitali University Hospital, Reykjavik, 
      Iceland.
FAU - Magnusson, Magnus K
AU  - Magnusson MK
AD  - Stem Cell Research Unit, Biomedical Center, Faculty of Medicine, University of 
      Iceland, Reykjavik, Iceland.
AD  - Department of Laboratory Hematology, Landspitali University Hospital, Reykjavik, 
      Iceland.
AD  - Department of Respiratory Medicine and Sleep, Landspitali University Hospital, 
      Reykjavik, Iceland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150921
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (CKAP4 protein, human)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Bronchi/*pathology
MH  - Case-Control Studies
MH  - Cell Line
MH  - Cell Plasticity
MH  - *Epithelial-Mesenchymal Transition
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/*pathology
MH  - Membrane Proteins/metabolism
MH  - Mesoderm
MH  - Phenotype
EDAT- 2015/09/22 06:00
MHDA- 2016/03/19 06:00
CRDT- 2015/09/22 06:00
PHST- 2014/12/02 00:00 [received]
PHST- 2015/07/17 00:00 [revised]
PHST- 2015/07/29 00:00 [accepted]
PHST- 2015/09/22 06:00 [entrez]
PHST- 2015/09/22 06:00 [pubmed]
PHST- 2016/03/19 06:00 [medline]
AID - S0023-6837(22)01393-9 [pii]
AID - 10.1038/labinvest.2015.114 [doi]
PST - ppublish
SO  - Lab Invest. 2015 Dec;95(12):1418-28. doi: 10.1038/labinvest.2015.114. Epub 2015 
      Sep 21.