The current understanding of potential mechanisms involved in PGE2-mediated attenuation of lung fibrosis and fibroblast to myofibroblast differentiation could involve but not limited to: (1) PGE2 deficiency in fibrotic lungs; (2) modulation of PGE2 signaling via EP1-4 receptors regulating apoptosis and proliferation; (3) epigenetic regulation of EP receptors in fibrotic lungs; (4) Interaction between plasminogen activation and PGE2 generation; and (5) Modulation of cross-talk between PGE2/EP2/EP4 and TGF-β/TGF-βR1/TGF-βR2 signal transduction (Figure 1). The gene discussed is TGFBR1; the disease is pulmonary fibrosis.