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

Scientific Reports
Chiharu OtaMelanie Königshoff

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 repai...Continue Reading

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Citations

Mar 23, 2019·Expert Opinion on Biological Therapy·Jonathan L McQualter
Jul 25, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tingting ZhangJian Tian
Aug 20, 2019·ERJ Open Research·Pitchumani SivakumarJason D Christie
May 31, 2020·Respiratory Research·Xiaofei CongXiaoli Zhao
Sep 30, 2020·American Journal of Respiratory Cell and Molecular Biology·Kun HanXuebin Qin
Nov 7, 2020·Biomaterials·Sally Yunsun KimCharlotte H Dean
Sep 23, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Amy Stieler StewartLiara M Gonzalez
Dec 23, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Debbie ClementsSimon R Johnson

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Datasets Mentioned

BETA
AB3786

Methods Mentioned

BETA
flow cytometry
transfections
FACS

Software Mentioned

Graph Pad Prism
FlowJo
ZEN2009
NDP
view2
ImageJ

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