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 TGFß1 signalling, is discussed.

The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator.

Survivin (also known as BIRC5) is a cancer-associated protein that exists in several locations in the cell. Its cytoplasmic residence in interphase cells is governed by CRM1 (also known as XPO1)-mediated nuclear exportation, and its localisation during mitosis to the centromeres and midzone microtubules is that of a canonical chromosomal passenger protein. In addition to these well-established locations, survivin is also a mitochondrial protein, but how it gets there and its function therein is presently unclear. Here, we show that the first ten amino acids at the N-terminus of survivin are sufficient to target GFP to the mitochondria in vivo, and ectopic expression of this decapeptide decreases cell adhesion and accelerates proliferation. The data support a signalling mechanism in which this decapeptide regulates the tyrosine kinase Src, leading to reduced focal adhesion plaques and disruption of F-actin organisation. This strongly suggests that the N-terminus of survivin is a mitochondrial-targeting sequence that regulates Src, and that survivin acts in concert with Src to promote tumorigenesis.