Figure 1.

Prostaglandin E2 signaling via EP2/EP4 in epithelial cells and fibroblasts for the development of pulmonary fibrosis. Schema depicts PGE2 biosynthesis from arachidonic acid by COX2 and prostaglandin E synthases in alveolar epithelial cells. The autacoid function of PGE2 via its receptors EP2 and EP4 regulates homeostatic signaling between the alveolar epithelial cells (AECs) and pulmonary fibroblasts. Fibrotic signaling is specified by enhanced apoptosis and diminished secretion of PGE2 by AECs due to injury, which in turn promotes fibroblast proliferation, collagen deposition, and myofibroblast differentiation, distinct in pulmonary fibrosis. AA—Arachidonic acid, cAMP—cyclic adenosine monophosphate, COX2—Cyclooxygenase-2, EP_2,4—Prostaglandin EP₂,EP₄ receptor, EPAC—Exchange protein directly activated by cAMP, PC—Phosphatidyl choline, PGE2—Prostaglandin E2, PGH2—Prostaglandin H2, PKA—Protein kinase A, PTGES—Prostaglandin E Synthase, PTEN—Phosphatase and tensin homolog.