Renal prostaglandin E2 receptor (EP) expression profile is altered in streptozotocin and B6-Ins2Akita type I diabetic mice.

摘要

The homeostatic function of prostaglandin E(2) (PGE(2)) is dependent on a balance of EP receptor-mediated events. A disruption in this balance may contribute to the progression of renal injury. Although PGE(2) excretion is elevated in diabetes, the expression of specific EP receptor subtypes has not been studied in the diabetic kidney. Therefore, the purpose of this study was to characterize the expression profile of four EP receptor subtypes (EP(1-4)) in 16-wk streptozotocin (STZ) and B6-Ins2(Akita) type I diabetic mice. In diabetic mice, the ratio of kidney weight to body weight was increased twofold compared with controls, blood glucose was elevated, but urine albumin was only increased in B6-Ins2(Akita) mice. The excretion of PGE(2) and its metabolite was augmented two- to fourfold as determined by enzyme immunoassay. Accordingly, renal cyclooxygenases were also increased in diabetic mice, with isoform-specific and regional differences in each model. Finally, there was altered EP(1-4) receptor expression in diabetic kidneys, with significant differences between STZ and B6-Ins2(Akita) mice (fold-control). In STZ mice, cortical EP(1) increased by 1.6, EP(3) increased by 2.3, and EP(4) decreased by 0.63; yet in B6-Ins2(Akita) mice, cortical EP(1) increased by 2.4, but there was a general decrease in the remaining subtypes. Similarly, in the STZ medulla EP(3) increased by 3.6, but both EP(1) and EP(3) increased by 5.5 and 1.95, respectively, in B6-Ins2(Akita) mice. Therefore, knowing the pattern of change in relative EP receptor expression in the kidney could be useful in identifying specific EP targets for the prevention of various components of diabetic kidney disease.