Physiological and pathophysiological implications of PGE2 and the PGE2 synthases in the kidney

Prostaglandin E-2 (PGE(2)) is the most abundant prostanoid synthesized in the kidney and plays an important role in renal function. Physiologically, PGE(2) regulates renal hemodynamics, water and sodium metabolism, blood pressure, and so on. As a well-known proinflammatory lipid mediator, PGE(2) also substantially mediates renal injury under many pathophysiological conditions. Multiple enzymes are involved in renal PGE(2) biosynthesis, including the three main PGE(2) terminal synthases, i.e. microsomal PGE(2) synthase-1 (mPGES-1), mPGES-2 and cytosolic PGE(2) synthase (cPGES). In the kidney, mPGES-1 is highly expressed in the collecting duct where it is the dominant contributor of PGE(2) biosynthesis and participates in blood pressure regulation and renal hemodynamic maintenance. mPGES-2 protein is mainly expressed in the renal cortex and the outer stripe of the outer medulla. cPGES is diffusely expressed in all nephron segments. Roles of mPGES-2 and cPGES in renal function have not been clearly characterized. Here we summarize the role of PGE(2) in the kidney, highlight the contribution of the three PGE(2) synthases, particularly mPGES-1, in blood pressure regulation and renal hemodynamics, and outline the contribution of mPGES-1 to kidney diseases. A clearer understanding of the role of PGE(2) in the kidney could pave the way for development of new therapeutic approaches.