Does ATP via purinergic receptor signalling fuel pulmonary fibrosis?

Background: Interstitial lung diseases (ILD) are poorly understood disorders characterised by diffuse damage to the lung parenchyma, with inflammation and fibrosis. Some manifest a progressive fibrotic phenotype with high fatality and limited treatment options, such as idiopathic pulmonary fibrosis (IPF).

Summary: The degree to which inflammation plays a role in fibrosis progression is unknown. However, wound healing and fibrosis are intricate processes influenced by various inflammatory factors. Extracellular nucleosides and nucleotides, including adenosine triphosphate (ATP), activate pro-inflammatory responses of innate immunity and are widely implicated in tissue fibrosis across different organs. The pro-inflammatory effects of extracellular nucleotides occur via P1 and P2 purinergic receptors, expressed across the lung and immune system, and have been implicated in various pulmonary diseases including pulmonary fibrosis. This review amalgamates available data on the complex role of P1 and P2 purinergic receptor signalling in pulmonary fibrosis and discusses perspectives for novel treatments.

Key Messages: Purinergic signalling plays a complex and pivotal role in pulmonary fibrosis, warranting further study. The intricate interplay between P1 and P2 receptor pathways necessitates a comprehensive approach to understand their collective impact. While evidence from preclinical models is promising, human studies are essential for further understanding in pulmonary fibrosis. Advances in receptor-specific agonists and antagonists provide novel avenues for research and may ultimately lead to new therapies for patients.