Press Release

Lung Research

Wnt receptor discovered as potential therapeutic target for lung fibrosis

Together with colleagues from the University of Groningen, scientists at the Helmholtz Zentrum München, partner in the German Center for Lung Research (DZL), have identified a specific receptor of the Wnt signalling pathway* as a therapeutic target for idiopathic pulmonary fibrosis (IPF). The results have recently been published in the FASEB Journal.

Königshoff & Baarsma

Dr. Dr. Melanie Königshoff and Dr. Hoeke Baarsma, Source: Helmholtz Zentrum München

Working with clinical partners, a team headed by Dr. Dr. Melanie Königshoff and Dr. Hoeke Baarsma at the Helmholtz Zentrum München Comprehensive Pneumology Center has now succeeded in detecting a novel function of the Frizzled-8 (FZD8) receptor. This receptor plays a role in the Wnt signalling pathway, which in turn can influence the development and progression of various diseases.

"Our research shows that FZD8 activation is involved in changing cell signalling pathways that play a role in the development of fibrotic diseases and possibly also other chronic lung diseases," says Baarsma. In particular the researchers were able to observe that the TGF-beta and Wnt signalling pathways act together via FZD8. The result is fibroblast activation and alteration of lung tissue, both of which are typical hallmarks for the development of idiopathic pulmonary fibrosis.

Inhibition of FZD8 as a therapeutic approach

According to the World Health Organization (WHO), chronic pulmonary diseases, such as idiopathic pulmonary fibrosis, are the world's second most common cause of death. Until now there have been few causal therapeutic approaches.

"The newly discovered effect of the FZD8 receptor on fibroblasts offers us the possibility to target treatment at an important interface between the Wnt and TGF-b signalling pathways and to inhibit the receptor," explains Königshoff, the study leader.

The research into therapies for the treatment of IPF and other chronic lung diseases is very important in order to offer prospects to patients with these sometimes very rapidly progressing illnesses. In addition to the Helmholtz Zentrum München, the Dutch Longfond also is funding the team of Melanie Königshoff, Hoeke Baarsma and the colleagues from Groningen for their investigation of innovative pharmacological approaches to intervene with Wnt signalling activity.

Scientists are attempting to further decode the involvement of FZD8 in disease development using modelling systems for chronic pulmonary diseases. Dr. Baarsma's research is focusing on the role of the Wnt signalling pathway on fibroblasts. His research project is funded by the Helmholtz Association as part of the Helmholtz post-doctoral programme.

Further information

The Wnt signalling pathway is one of many pathways for the transmission of signals that allow cells to respond to external changes. The signalling pathway is named after its main player "Wnt", a signalling protein that takes on a key function in the development of various animal cells as a local mediator. Numerous proteins, including beta-catenin, are involved in transmitting the signals.

Original publication:
Spanjer, AI et al. (2016): TGF-β-induced profibrotic signaling is regulated in part by the WNT receptor Frizzled-8. FASEB Journal, doi: 10.1096/fj.201500129

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München 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.

The Comprehensive Pneumology Center (CPC) is a joint research project of the Helmholtz Zentrum München, the Ludwig-Maximilians-Universität with its University Hospital and the Asklepios Fachkliniken München-Gauting. The CPC's objective is to conduct research on chronic lung diseases in order to develop new diagnosis and therapy strategies. The CPC maintains a focus on experimental pneumology with the investigation of cellular, molecular and immunological mechanisms involved in lung diseases. The CPC is one of five sites of the German Center for Lung Research (Deutsches Zentrum für Lungenforschung,  DZL).

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.

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