The role of the Transient Receptor Potential (TRP) channels in virus-induced lung fibrosis

• Applicant: Professor Dr. Heiko Adler
• Subject Area: Pharmacology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556389272

Idiopathic pulmonary fibrosis (IPF) is the most devastating interstitial lung disease (ILD), frequently accompanied by additional co-morbidities including coronary arteriosclerosis, venous thromboembolic disease and lung cancer, all having a severe impact on the quality of life and a high mortality rate. Death usually ensues 2-5 years after diagnosis due to respiratory failure. The underlying cause of IPF is not known but viral infections have been suggested as a trigger driving the susceptibility for IPF. In line with this, it is expected that post-COVID lung fibrosis will become a huge medical and public health issue. Thus, the demand for the development of efficient therapies to fight against lung fibrosis remains challenging, despite of the recent approval of nintedanib and pirfenidone for the treatment of IPF patients. Both drugs slow down disease progression but do not reverse or even block the course of the disease and induce adverse effects in IPF patients. Currently, the only curative therapy remains organ transplantation, and new drugs with fewer adverse effects are highly desirable. Thus, there is a great medical need to better understand the mechanisms by which viral infections lead to lung fibrosis in order to develop new therapeutic options to treat and fight this deadly disease. A very attractive target for the development of new therapies for the treatment of virus-induced lung fibrosis are Transient Receptor Potential (TRP) channels. TRP channels are druggable, and a variety of agonists and antagonists which might be eligible for repurposing, are already available. In the lung, a variety of TRP channels is expressed where they may act as toxicant sensors as well as mediators of lung inflammation and associated diseases including IPF. TRP channel dysfunction or hyperactivity may also impact lung function and lung diseases related to infections. Therefore, in this project, we want to elucidate the role of TRP channels, in particular TRPV2 predominantly expressed in lung macrophages, as future therapeutic targets in virus-induced lung fibrosis. To this end, we will investigate the role of TRPV2 during lung infection and fibrosis with a particular focus on lung macrophages. We will use a comprehensive research approach, combining in vitro studies with isolated primary lung macrophages and in vivo experiments in a mouse model of virus-induced pulmonary fibrosis.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Alexander Dietrich