Format

Send to

Choose Destination
Cell Mol Life Sci. 2019 Mar 18. doi: 10.1007/s00018-019-03067-8. [Epub ahead of print]

A critical role for miR-142 in alveolar epithelial lineage formation in mouse lung development.

Author information

1
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
2
Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University Giessen, 35392, Giessen, Germany.
3
Department of Medicine, Cedars-Sinai Medical Center, Lung and Regenerative Medicine Institutes, Los Angeles, CA, USA.
4
Centre National de la Recherche Scientifique, CNRS, UMR 7275, Institut de Pharmacologie Moleculaire et Cellulaire (IPMC), Sophia Antipolis, France.
5
Universite Cote d'Azur, Nice, France.
6
Lung Cancer Epigenetics, Member of the German Center of Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.
7
Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008, Kazan, Russian Federation.
8
Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
9
Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang, People's Republic of China.
10
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Cho-Ming.Chao@paediat.med.uni-giessen.de.
11
Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University Giessen, 35392, Giessen, Germany. Cho-Ming.Chao@paediat.med.uni-giessen.de.
12
Department of General Pediatrics and Neonatology, University Children's Hospital Gießen, Justus-Liebig-University, Giessen, Germany. Cho-Ming.Chao@paediat.med.uni-giessen.de.
13
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. saverio.bellusci@innere.med.uni-giessen.de.
14
Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig-University Giessen, 35392, Giessen, Germany. saverio.bellusci@innere.med.uni-giessen.de.

Abstract

The respiratory epithelium arises from alveolar epithelial progenitors which differentiate into alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. AT2 cells are stem cells in the lung critical for the repair process after injury. Mechanisms regulating AT1 and AT2 cell maturation are poorly defined. We report that the activation of the glucocorticoid pathway in an in vitro alveolar epithelial lineage differentiation assay led to increased AT2 marker Sftpc and decreased miR-142 expression. Using miR-142 KO mice, we demonstrate an increase in the AT2/AT1 cell number ratio. Overexpression of miR-142 in alveolar progenitor cells in vivo led to the opposite effect. Examination of the KO lungs at E18.5 revealed enhanced expression of miR-142 targets Apc, Ep300 and Kras associated with increased β-catenin and p-Erk signaling. Silencing of miR-142 expression in lung explants grown in vitro triggers enhanced Sftpc expression as well as increased AT2/AT1 cell number ratio. Pharmacological inhibition of Ep300-β-catenin but not Erk in vitro prevented the increase in Sftpc expression triggered by loss of miR-142. These results suggest that the glucocorticoid-miR-142-Ep300-β-catenin signaling axis controls pneumocyte maturation.

KEYWORDS:

Alveolar epithelium; Beta-catenin; EP300; Lung; microRNA-142

PMID:
30887098
DOI:
10.1007/s00018-019-03067-8

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center