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Cell Stem Cell. 2017 Feb 2;20(2):261-273.e3. doi: 10.1016/j.stem.2016.10.004. Epub 2016 Nov 17.

Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis.

Author information

1
Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
2
Department of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO 80206, USA.
3
Ludwig Boltzmann Institute for Lung Vascular Research, Center for Medical Research, 8010 Graz, Austria.
4
Institute of Biotechnology, FinMIT Cluster of Excellence, Viikinkaari 5, FI-00790 Helsinki, Finland.
5
Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Justus-Liebig-University Giessen, 35392 Giessen, Germany; Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute, 61231 Bad Nauheim, Germany.
6
Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute, 61231 Bad Nauheim, Germany.
7
Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Justus-Liebig-University Giessen, 35392 Giessen, Germany; College of Life and Environmental Sciences, Wenzhou University, Wenzhou, Zhejiang, China. Electronic address: saverio.bellusci@innere.med.uni-giessen.de.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a form of progressive interstitial lung disease with unknown etiology. Due to a lack of effective treatment, IPF is associated with a high mortality rate. The hallmark feature of this disease is the accumulation of activated myofibroblasts that excessively deposit extracellular matrix proteins, thus compromising lung architecture and function and hindering gas exchange. Here we investigated the origin of activated myofibroblasts and the molecular mechanisms governing fibrosis formation and resolution. Genetic engineering in mice enables the time-controlled labeling and monitoring of lipogenic or myogenic populations of lung fibroblasts during fibrosis formation and resolution. Our data demonstrate a lipogenic-to-myogenic switch in fibroblastic phenotype during fibrosis formation. Conversely, we observed a myogenic-to-lipogenic switch during fibrosis resolution. Analysis of human lung tissues and primary human lung fibroblasts indicates that this fate switching is involved in IPF pathogenesis, opening potential therapeutic avenues to treat patients.

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PMID:
27867035
PMCID:
PMC5291816
DOI:
10.1016/j.stem.2016.10.004
[Indexed for MEDLINE]
Free PMC Article

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