COX-2 but Not mPGES-1 Contributes to Renal PGE2 Induction and Diabetic Proteinuria in Mice with Type-1 DiabetesReportar como inadecuado

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Prostaglandin E2 PGE2 has been implicated to play a pathogenic role in diabetic nephropathy DN but its source remains unlcear. To elucidate whether mPGES-1, the best characterized PGE2 synthase, was involved in the development of DN, we examined the renal phenotype of mPGES-1 KO mice subjected to STZ-induced type-1 diabetes. After STZ treatment, mPGES-1 WT and KO mice presented the similar onset of diabetes as shown by similar elevation of blood glucose. Meanwhile, both genotypes of mice exhibited similar increases of urinary and renal PGE2 production. In parallel with this comparable diabetic status, the kidney injury indices including the urinary albumin excretion, kidney weight and the kidney histology PAS staining did not show any difference between the two genotypes. By Western-blotting and quantitative qRT-PCR, mPGES-1, mPGES-2, cPGES and 15-hydroxyprostaglandin dehydrogenase 15-PGDH remain unaltered following six weeks of diabetes. Finally, a selective COX-2 inhibitor celecoxib 50 mg-kg-day was applied to the STZ-treated KO mice, which resulted in significant reduction of urinary albumin excretion KO-STZ: 141.5±38.4 vs. KO-STZ + Celebrex: 48.7±20.8 ug-24 h, p<0.05 and the blockade of renal PGE2 induction kidney: KO-STZ: 588.7±89.2 vs. KO-STZ + Celebrex: 340.8±58.7 ug-24 h, p<0.05; urine: KO-STZ 1667.6±421.4 vs. KO-STZ + Celebrex 813.6±199.9 pg-24 h, p<0.05, without affecting the blood glucose levels and urine volume. Taken together, our data suggests that an as yet unidentified prostaglanind E synthase but not mPGES-1 may couple with COX-2 to mediate increased renal PGE2 sythsesis in DN.

Autor: Zhanjun Jia , Ying Sun , Shanshan Liu, Ying Liu, Tianxin Yang



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