Involvement of P2R signalling in the pathogenesis of fibrotic lung diseases

• Applicant: Dr. Tobias Müller
• Subject Area: Pneumology, Thoracic Surgery
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 221560265

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Currently, there is no effective therapy available. The pathogenesis of this devastating disease is not fully understood. In the past, extracellular nucleotides, e. g. adenosine-5’-triphosphate (ATP) have gained attention as mediators of inflammation and immuno-regulation via purinergic receptor (P2R) signalling. Preliminary results showed that extracellular ATP levels are elevated in patients suffering from IPF or after the induction of experimental lung fibrosis in mice. Furthermore, treatment of these animals with non-selective P2R antagonists led to reduced inflammation and fibrosis. The aim of this project is to identify the P2R subtypes involved in the pathogenesis of both bleomycin-induced lung fibrosis in mice and IPF in humans. Therefore, P2R deficient mice as well as specific P2R antagonists will be used. Additionally, fibroblast migration and intracellular signalling in response to different nucleotides will be investigated. To confirm the relevance of the results obtained in animal experiments for the situation in humans, P2R expression on broncho-alveolar lavage and blood cells from IPF patients will be compared to healthy individuals. These studies will provide important information about the pathophysiology of pulmonary fibrosis and could open a new therapeutic approach for the treatment of fibrotic lung diseases.

• DFG Programme: Research Grants