1. Urinary excretions of lipocalin-type prostaglandin D2 synthase predict the development of proteinuria and renal injury in OLETF rats.
- Author
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Ogawa M, Hirawa N, Tsuchida T, Eguchi N, Kawabata Y, Numabe A, Negoro H, Hakamada-Taguchi R, Seiki K, Umemura S, Urade Y, and Uehara Y
- Subjects
- Animals, Chromans pharmacology, Diabetes Mellitus, Type 2 urine, Hypoglycemic Agents pharmacology, Immunoenzyme Techniques, Intramolecular Oxidoreductases genetics, Lipocalins, RNA, Messenger metabolism, Rats, Rats, Inbred OLETF, Thiazolidinediones pharmacology, Troglitazone, Diabetic Nephropathies urine, Intramolecular Oxidoreductases urine, Proteinuria urine, Renal Insufficiency urine
- Abstract
Background: Otsuka Long-Evans Tokushima Fatty (OLETF) rats genetically develop diabetes which is associated with hypertension. In preliminary studies, urinary excretions of L-PGDS (lipocaline-type prostaglandin D synthase) increase before diabetic nephropathy obviously develops, and this may predict progression of renal injury following diabetes. In the present study, we attempted to define whether urinary excretions of L-PGDS behave as the predictor of development of diabetic nephropathy in OLETF rats., Methods: We investigated alterations of urinary L-PGDS excretions during the establishment of diabetes and assessed the relationship between the L-PGDS excretions and renal function in OLETF rats. Furthermore, we treated OLETF rats with troglitazone and analysed the effects on L-PGDS metabolisms. Urinary L-PGDS was measured by immunoenzyme assay and the occurrence of L-PGDS and its mRNA in the kidney was assessed by immunohistochemistry and a PCR method., Results: Urinary excretions of L-PGDS were significantly higher in OLETF rats than non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. The excretions age-dependently increased in OLETF and this increase appeared to be due to increased glomerular permeability to L-PGDS. Messenger RNA and antigenicity of L-PGDS were demonstrated in renal tissue; however, the de novo synthesis of L-PGDS mRNA seemingly contributed to urinary L-PGDS excretions much less than glomerular filtration. Multiple regression analysis revealed that urinary L-PGDS was determined by urinary protein excretions, and not by high blood pressure per se. Conversely, urinary proteinuria in the established diabetic nephropathy was predicted by urinary L-PGDS excretions in the early stage of diabetes., Conclusions: Urinary excretions of L-PGDS are likely to reflect the underlying increase in glomerular permeability. This property may be useful to predict forthcoming glomerular damage following diabetes in OLETF rats.
- Published
- 2006
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