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Dynamic expression of HOPX in alveolar epithelial cells reflects injury and repair during the progression of pulmonary fibrosis

Ota, Chiharu; Ng-Blichfeldt, John-Poul; Korfei, Martina; Alsafadi, Hani N. LU ; Lehmann, Mareike; Skronska-Wasek, Wioletta; De Santis, Martina M. LU ; Guenther, Andreas; Wagner, Darcy LU and Königshoff, Melanie (2018) In Scientific Reports 8.
Abstract
Mechanisms of injury and repair in alveolar epithelial cells (AECs) are critically involved in the progression of various lung diseases including idiopathic pulmonary fibrosis (IPF). Homeobox only protein x (HOPX) contributes to the formation of distal lung during development. In adult lung, alveolar epithelial type (AT) I cells express HOPX and lineage-labeled Hopx+ cells give rise to both ATI and ATII cells after pneumonectomy. However, the cell function of HOPX-expressing cells in adult fibrotic lung diseases has not been investigated. In this study, we have established a flow cytometry-based method to evaluate HOPX-expressing cells in the lung. HOPX expression in cultured ATII cells increased over culture time, which was accompanied by... (More)
Mechanisms of injury and repair in alveolar epithelial cells (AECs) are critically involved in the progression of various lung diseases including idiopathic pulmonary fibrosis (IPF). Homeobox only protein x (HOPX) contributes to the formation of distal lung during development. In adult lung, alveolar epithelial type (AT) I cells express HOPX and lineage-labeled Hopx+ cells give rise to both ATI and ATII cells after pneumonectomy. However, the cell function of HOPX-expressing cells in adult fibrotic lung diseases has not been investigated. In this study, we have established a flow cytometry-based method to evaluate HOPX-expressing cells in the lung. HOPX expression in cultured ATII cells increased over culture time, which was accompanied by a decrease of proSP-C, an ATII marker. Moreover, HOPX expression was increased in AECs from bleomycin-instilled mouse lungs in vivo. Small interfering RNA-based knockdown of Hopx resulted in suppressing ATII-ATI trans-differentiation and activating cellular proliferation in vitro. In IPF lungs, HOPX expression was decreased in whole lungs and significantly correlated to a decline in lung function and progression of IPF. In conclusion, HOPX is upregulated during early alveolar injury and repair process in the lung. Decreased HOPX expression might contribute to failed regenerative processes in end-stage IPF lungs. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
8
publisher
Nature Publishing Group
external identifiers
  • scopus:85052401221
ISSN
2045-2322
DOI
10.1038/s41598-018-31214-x
language
English
LU publication?
yes
id
62e5323c-f743-4ec5-91a0-30670f53dc00
date added to LUP
2018-08-28 15:01:32
date last changed
2019-01-06 14:02:51
@article{62e5323c-f743-4ec5-91a0-30670f53dc00,
  abstract     = {Mechanisms of injury and repair in alveolar epithelial cells (AECs) are critically involved in the progression of various lung diseases including idiopathic pulmonary fibrosis (IPF). Homeobox only protein x (HOPX) contributes to the formation of distal lung during development. In adult lung, alveolar epithelial type (AT) I cells express HOPX and lineage-labeled Hopx+ cells give rise to both ATI and ATII cells after pneumonectomy. However, the cell function of HOPX-expressing cells in adult fibrotic lung diseases has not been investigated. In this study, we have established a flow cytometry-based method to evaluate HOPX-expressing cells in the lung. HOPX expression in cultured ATII cells increased over culture time, which was accompanied by a decrease of proSP-C, an ATII marker. Moreover, HOPX expression was increased in AECs from bleomycin-instilled mouse lungs in vivo. Small interfering RNA-based knockdown of Hopx resulted in suppressing ATII-ATI trans-differentiation and activating cellular proliferation in vitro. In IPF lungs, HOPX expression was decreased in whole lungs and significantly correlated to a decline in lung function and progression of IPF. In conclusion, HOPX is upregulated during early alveolar injury and repair process in the lung. Decreased HOPX expression might contribute to failed regenerative processes in end-stage IPF lungs.},
  articleno    = {12983},
  author       = {Ota, Chiharu and Ng-Blichfeldt, John-Poul and Korfei, Martina and Alsafadi, Hani N. and Lehmann, Mareike and Skronska-Wasek, Wioletta and De Santis, Martina M. and Guenther, Andreas and Wagner, Darcy and Königshoff, Melanie},
  issn         = {2045-2322},
  language     = {eng},
  month        = {08},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Dynamic expression of HOPX in alveolar epithelial cells reflects injury and repair during the progression of pulmonary fibrosis},
  url          = {http://dx.doi.org/10.1038/s41598-018-31214-x},
  volume       = {8},
  year         = {2018},
}