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.