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

Prostaglandin E2 (PGE2) is the most abundant prostanoid synthesized in the kidney and plays an important role in renal function. Physiologically, PGE2 regulates renal hemodynamics, water and sodium metabolism, blood pressure, and so on. As a well-known proinflammatory lipid mediator, PGE2 also substantially mediates renal injury under many pathophysiological conditions. Multiple enzymes are involved in renal PGE2 biosynthesis, including the three main PGE2 terminal synthases, i.e. microsomal PGE2 synthase-1 (mPGES-1), mPGES-2 and cytosolic PGE2 synthase (cPGES). In the kidney, mPGES-1 is highly expressed in the collecting duct where it is the dominant contributor of PGE2 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 PGE2 in the kidney, highlight the contribution of the three PGE2 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 PGE2 in the kidney could pave the way for development of new therapeutic approaches.