Immunohistochemical Expressions of Main PGE₂ Biosynthesis-related Enzymes and PGE₂ Receptor in Rat Nephrogenesis

Abstract

Endogenous prostaglandin (PG) E₂ plays important roles in renal homeostasis. Immunoexpressions of PGE₂ biosynthesis-related enzymes, cyclooxygenase (COX)-2 and microsomal PGE₂ synthetase (mPGES)-1 and EP4 (a PGE₂ receptor), were investigated in renal development. Kidney tissues were obtained from fetuses on gestation days 18 and 21 and neonates on days 1 to 18. In fetuses and early neonates, the expressions of COX-2, mPGES-1 and EP4 were observed in developing renal tubules, indicating that COX-2 and its product, PGE₂, play important roles in blastemal cell-derived renal tubular development via EP4. Cyclin D1 expression was seen in both the nucleus and cytoplasm of the developing tubules. These findings differed from the decreased COX-2 expression and exclusive nuclear expression of cyclin D1 seen in abnormal epithelial regeneration of injured renal tubules in cisplatin-treated rats in our previous articles. Collectively, PGE₂, induced by COX-2, regulates renal tubular epithelial formation via EP4.