Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

COPD – what causes the lungs to lose their ability to heal?

16.12.2016

In chronic obstructive pulmonary disease (COPD), the patients’ lungs lose their ability to repair damages on their own. Scientists at the Helmholtz Zentrum München, partner in the German Center for Lung Research (DZL) now have a new idea as to why this might be so. In the ‘Journal of Experimental Medicine’, they blame the molecule Wnt5a for this problem. Plese find a video with the study leader Melanie Königshoff here https://vimeo.com/192428939

The first indication of COPD is usually a chronic cough. As the disease progresses, the airways narrow and often pulmonary emphysema develops. This indicates irreversible expansion and damage to the alveoli, or air sacks. "The body is no longer able to repair the destroyed structures," explains Dr. Dr. Melanie Königshoff, head of the Research Unit Lung Repair and Regeneration (LRR) at the Comprehensive Pneumology Center (CPC) of Helmholtz Zentrum München. She and her team have made it their job to understand how this happens.


The molecule Wnt5a prevents the repair of structures in the lung of COPD patients. Shown here are the alveolar epithelium (green) and immune cells (red).

Source: Helmholtz Zentrum München


Dr. Dr. Melanie Königshoff and Dr. Hoeke Baarsma

Source: Helmholtz Zentrum München

"In our current work we have been able to show that COPD results in a change in the messengers that lung cells use to communicate with one another," Königshoff continues. Specifically, the scientists discovered increased production of the Wnt5a molecule, which disrupts the classic (or canonical, as the experts call it) Wnt/beta-catenin signaling pathway* that is responsible for such repairs.

"Our working hypothesis was that the relationship between different Wnt messengers is no longer balanced in COPD," reports Dr. Hoeke Baarsma, LRR scientist and the study’s first author. The team correspondingly searched for possible interference signals. "In both the pre-clinical model and the tissue samples from patients, we found that in COPD tissue particularly the non-canonical Wnt5a molecule is increased and occurs in a modified form." According to the authors, stimuli that typically cause a reaction in COPD, such as cigarette smoke, additionally lead to increased production of Wnt5a and consequently to impaired lung regeneration.

In the next step, the researchers were able to show where the misdirected signal originates: "It is produced by certain cells in the connective tissue, the so-called fibroblasts," Baarsma says. When pulmonary epithelial cells were treated with the Wnt5a derived from the fibroblasts, the cells lost their healing ability. The scientists were also able to use antibodies directed against Wnt5a in two different experimental models to slow down the lung destruction and better maintain the lung function.

"Our results show that the classic Wnt/beta-catenin signal cascade is disrupted by the Wnt5a ligand. This is a completely new mechanism in association with COPD and could lead to new therapeutic approaches, which are urgently needed for treatment," study leader Königshoff explains the importance of the results.

Further information

* The Wnt signaling pathway is one of many pathways for forwarding signals in order to allow cells to respond to external changes. The signaling pathway is named after its main player "Wnt", a signaling protein that takes on a key function in the development of various animal cells as a local mediator. Numerous proteins are involved in the canonical (classic) forwarding of the signals, including beta-catenin as the central cellular messenger. A pathway in which Wnt acts through other messengers, as described here, is called a non-canonical signaling pathway; this can have a negative impact on the canonical signaling.

Background: Melanie Königshoff’s department is a part of the German Center for Lung Research (Deutsches Zentrum für Lungenforschung - DZL). Dr. Hoeke Baarsma works as a post-doctoral scientist in the framework of the PFP program, which is sponsored by the Helmholtz Association.

Original publication: Baarsma, HA et al. (2016): Non-canonical WNT-5A signaling impairs 1 endogenous lung repair in COPD. Journal of Experimental Medicine, doi: 10.1084/jem.20160675

Related article:
Wnt receptor discovered as potential therapeutic target for lung fibrosis
https://www.helmholtz-muenchen.de/en/press-media/press-releases/2016/press-relea...

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en

The Lung Repair and Regeneration Research Unit is part of the Comprehensive Pneumology Center (CPC), which is a joint undertaking of the Helmholtz Zentrum München, Ludwig Maximilian University Munich with its University Hospital, and the Asklepios Specialist Clinics Munich-Gauting. The CPC's objective is to conduct research on chronic lung diseases in order to develop new diagnostic tools and therapies. The LRR Research Unit examines new mechanisms and repair processes in the lungs for a better understanding that will allow the development of new therapeutic approaches. The unit also focuses on developing new methods in order to reduce the gap between pre-clinical research and its application on patients. The CPC is a facility of the German Center for Lung Research (Deutsches Zentrum für Lungenforschung - DZL). http://www.helmholtz-muenchen.de/lrr

The German Center for Lung Research (DZL) pools German expertise in the field of pulmonology research and clinical pulmonology. The association’s head office is in Giessen. The aim of the DZL is to find answers to open questions in research into lung diseases by adopting an innovative, integrated approach and thus to make a sizeable contribution to improving the prevention, diagnosis and individualized treatment of lung disease and to ensure optimum patient care. http://www.dzg-lungenforschung.de

Contact for the media:
Department of Communication, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel. +49 89 3187 2238 - Fax: +49 89 3187 3324 - E-mail: presse@helmholtz-muenchen.de

Scientific contact:
Dr. Dr. Melanie Königshoff, Helmholtz Zentrum München - German Research Center for Environmental Health, Comprehensive Pneumology Center, Max-Lebsche-Platz 31, 81377 München, Germany - Tel. +49 89 3187 4668 - E-mail: melanie.koenigshoff@helmholtz-muenchen.de

Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

Further reports about: COPD DZL Environmental Health Helmholtz Pneumology Wnt5a lung diseases signaling pathway

More articles from Health and Medicine:

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

nachricht Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>