Metformin induces lipogenic differentiation in myofibroblasts to reverse lung fibrosis

Vahid Kheirollahi, Roxana M. Wasnick, Valentina Biasin, Ana Ivonne Vazquez-Armendariz, Xuran Chu, Alena Moiseenko, Astrid Weiss, Jochen Wilhelm, Jin-San Zhang, Grazyna Kwapiszewska, Susanne Herold, Ralph T. Schermuly, Bernard Mari, Xiaokun Li, Werner Seeger, Andreas Günther, Saverio Bellusci () and Elie El Agha ()
Additional contact information
Vahid Kheirollahi: The First Affiliated Hospital of Wenzhou Medical University
Roxana M. Wasnick: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Valentina Biasin: Medical University Graz
Ana Ivonne Vazquez-Armendariz: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Xuran Chu: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Alena Moiseenko: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Astrid Weiss: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Jochen Wilhelm: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Jin-San Zhang: Wenzhou Medical University
Grazyna Kwapiszewska: Medical University Graz
Susanne Herold: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Ralph T. Schermuly: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Bernard Mari: UMR 7275
Xiaokun Li: Wenzhou Medical University
Werner Seeger: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Andreas Günther: Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen
Saverio Bellusci: The First Affiliated Hospital of Wenzhou Medical University
Elie El Agha: The First Affiliated Hospital of Wenzhou Medical University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease in which the intricate alveolar network of the lung is progressively replaced by fibrotic scars. Myofibroblasts are the effector cells that excessively deposit extracellular matrix proteins thus compromising lung structure and function. Emerging literature suggests a correlation between fibrosis and metabolic alterations in IPF. In this study, we show that the first-line antidiabetic drug metformin exerts potent antifibrotic effects in the lung by modulating metabolic pathways, inhibiting TGFβ1 action, suppressing collagen formation, activating PPARγ signaling and inducing lipogenic differentiation in lung fibroblasts derived from IPF patients. Using genetic lineage tracing in a murine model of lung fibrosis, we show that metformin alters the fate of myofibroblasts and accelerates fibrosis resolution by inducing myofibroblast-to-lipofibroblast transdifferentiation. Detailed pathway analysis revealed a two-arm mechanism by which metformin accelerates fibrosis resolution. Our data report an antifibrotic role for metformin in the lung, thus warranting further therapeutic evaluation.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10839-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10839-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10839-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().