title: Urinary excretions of lipocalin-type prostaglandin D2 synthase predict the development of proteinuria and renal injury in OLETF rats.
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.
authors.affiliation: Department of Medicine, Yokohama City University, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Ogawa
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hirawa
authors.forename: Takamasa
authors.initials: T
authors.lastname: Tsuchida
authors.forename: Naomi
authors.initials: N
authors.lastname: Eguchi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Numabe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Negoro
authors.forename: Rie
authors.initials: R
authors.lastname: Hakamada-Taguchi
authors.forename: Kousuke
authors.initials: K
authors.lastname: Seiki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Uehara
mesh_terms: D000818:Animals; D002839:Chromans / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000652:urine; D003928:Diabetic Nephropathies / Q000652:urine*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000652:urine*; D054834:Lipocalins; D011507:Proteinuria / Q000652:urine*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D051437:Renal Insufficiency / Q000652:urine*; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D002839:Chromans; D007004:Hypoglycemic Agents; D054834:Lipocalins; D012333:RNA, Messenger; D045162:Thiazolidinediones; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000077288:Troglitazone