In IPF there is increased abundance of profibrotic ligands, notably: LPA, endothelin, and serotonin that activate receptors coupled to Gαi/o, Gαq/11, Gα12/13 promoting multiple pathways including Rho and ROCK which regulates the actin cytoskeleton. MRTF-A/B and YAP/TAZ are cytoskeletal sensitive profibrotic transcription co-factors essential to fibroblast activation. Known transcript targets for MRTF and YAP/TAZ are profibrotic genes: COL1A1, COL1A2, CTGF,and ACTA2. GPCRs which couple to Gαs are antifibrotic and negatively regulate MRTF-A/B and YAP/TAZ, but are often repressed in IPF patient fibroblasts. Profibrotic signaling is shown in orange and antifibrotic signaling is show in blue.