Logo Professor for Acute Lung Injury

Chair for Internal Medicine, Infectious Diseases
and Pulmonary Research

Logo Universitätsklinikum Giessen Logo Justus Liebig Universität Giessen
Logo Professor for Acute Lung Injury

Chair for Pulmonary Infections

 

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

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.

El Agha E, Moiseenko A, Kheirollahi V, De Langhe S, Crnkovic S, Kwapiszewska G, Kosanovic D, Schwind F, Schermuly RT, Henneke I, MacKenzie B, Quantius J, Herold S, Ntokou A, Ahlbrecht K, Morty RE, Gunther A, Seeger W, Bellusci S

Cell Stem Cell , 2017 20(2): 261-73 e3.
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Susanne Herold, MD, PhD

Department of Medicine V

Internal Medicine, Infectious Diseases and Infection Control

University Hospital Giessen und Marburg (UKGM)

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D-35392 Giessen
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