Spatiotemporal regulation of anti-remodelling signalling pathways in primary human lung fibroblasts

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterised by fibrosis and scarring of lung tissue. Current approved therapeutics having limited efficacy and severe adverse effects. This thesis investigates the activation of the prostacyclin receptor (IPR), as a potential therapeutic approach for the treatment of IPF. Using targeted FRET biosensors to investigate cAMP and ERK signalling with high spatial and temporal resolution, a complex relationship was discovered between IPR signalling and phenotypic outcome The most significant result was the reversal of efficacy at phenotypically relevant readouts, demonstrating that sustained cAMP signalling may be important for IPF therapeutics.