Adenosine receptor signalling as a driver of pulmonary fibrosis

Pulmonary fibrosis is a debilitating and life-limiting lung condition in which the damage- response mechanisms of mixed-population cells within the lungs go awry. The tissue microenvironment is drastically remodelled by aberrantly activated fibroblasts which deposit ECM components into the surrounding lung tissue, detrimentally affecting lung function and capacity for gas exchange. Growing evidence suggests a role for adenosine signalling in the pathology of tissue fibrosis in a variety of organs, including the lung, but the molecular pathways through which this occurs remain largely unknown. This review explores the role of adenosine in fibrosis and evaluates the contribution of the different adenosine receptors to fibrogenesis. Therapeutic targeting of the adenosine receptors is also considered, along with clinical observations pointing towards a role for adenosine in fibrosis. In addition, the interaction between adenosine signalling and other profibrotic signalling pathways, such as TGFβ1 signalling, is discussed.