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Research at CPC-M - Extracellular vesicles against lung scarring

Research at CPC-M

Extracellular vesicles against lung scarring

Are bubbles outside the cell an important accomplice to fight against incurable idiopathic pulmonary fibrosis?

For many lung diseases, we still don´t understand exactly, what happens at the level of the cell. Idiopathic pulmonary fibrosis (IPF) for example is a particularly aggressive form of pulmonary fibrosis that progresses extremely rapidly. Unlike other fibrotic lung diseases, the cause of IPF is completely unclear (idiopathic = no identifiable cause). The symptoms are all the more serious: The lung tissue is scarred, the oxygen absorption is hindered, the lung function decreases.
At the cellular level, various mechanisms have been explored that lead to this scarring. Certain proteins contribute to the unwanted production of collagens. Autoimmune processes are also discussed as a contributing factor.

DZL researchers have now succeeded in proving a previously unknown player in this fateful game: extracellular vesicles.

A group headed by Prof. Melanie Königshoff, DZL-PI and head of the LRR Unit at the CPC-M (Research Unit Lung Repair and Regeneration) has been working on a specific signaling molecule for years. This molecule, WNT-5A, contributes to the progressive scarring of the lung in idiopathic pulmonary fibrosis and thus the worsening of the disease.

What the researchers also discovered: In IPF patients, WNT-5A is increasingly transported via small, fluid-filled vesicles. These vesicles are located outside the cell, therefore they are called Extracellular Vesicles.

Extracellular vesicles under the microscope

Extracellular vesicles under the microscope  © Helmholtz Zentrum München

Illustration of pulmonary fibrosis
© Angelika Kramer
Illustration Lung Fibrosis

The conclusion of the team was straight forward: if we "block the way” for WNT-5A, preventing it from being transported by the vesicles - does that also reduce the scarring of the lung tissue? Or is it even possible to change the content of the vesicles in a way that the messenger substances they contain have a therapeutic effect? In any case, WNT-5A should serve as a biomarker to determine the degree of idiopathic pulmonary fibrosis.

The team now wants to investigate these hypotheses in further preclinical studies.

For this work, the LRR team was awarded the price for the best basic scientific publication at the annual meeting of the DZL DPLD disease area in 2019.

Head of Research Unit

Prof. Dr. Dr. Melanie Königshoff

Helmholtz Zentrum München
Research Unit Lung Repair and Regeneration (LRR)
Max-Lebsche-Platz 31
81377 München

Team Assistant:

Daniela Haas
Tel: +49 89 3187-4065
E-Mail:
daniela.haas@helmholtz-muenchen.de

Team

Dr. Mareike Lehmann,
Postdoc/Head of Team
Dr. Katharina Heinzelmann, Postdoc
Aina Martin-Medina, Doctoral Student
Rita Costa, Doctoral Student
Qiangjiang Hu, Doctoral Student
Kathrin Hafner, Technical Assistant
Anastasia van den Berg,
Technical Assistant
Maria Magdalena Stein,
Technical Assistant

Publications

A. Martin-Medina et al, Am J Respir Crit Care Med., 2018:
Increased Extracellular Vesicles Mediate WNT-5A Signaling in Idiopathic Pulmonary Fibrosis.

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