title: Uninephrectomy of diabetic OVE26 mice greatly accelerates albuminuria, fibrosis, inflammatory cell infiltration and changes in gene expression.
abstract: OBJECTIVE
  OVE26 (OVE) mice provide a valuable model of advanced diabetic nephropathy (DN), but they take 8 months to develop moderate interstitial fibrosis and reduced glomerular filtration rate (GFR). The aim of this project was to produce a more rapid and advanced model of DN.
  
  
  METHODS
  Uninephrectomy was applied to OVE and FVB mice at 2 months of age. Albuminuria, GFR, glomerulosclerosis, interstitial fibrosis, gene expression and monocyte infiltration were evaluated as a function of diabetes and uninephrectomy.
  
  
  RESULTS
  Albuminuria, monocyte infiltration, mesangial matrix expansion and renal fibrosis were greatly accelerated in uninephrectomized mice. DN was more advanced 10 weeks after uninephrectomy than in untreated OVE mice at 8 months of age. Uninephrectomy had almost no effect on these characteristics in non-diabetic mice. Microarray studies indicated that the accelerated fibrosis and cell infiltration in nephrectomized OVE mice were accompanied by corresponding gene expression changes in canonical pathways for fibrosis and inflammation.
  
  
  CONCLUSIONS
  Uninephrectomy greatly accelerates all features of diabetic renal damage. This procedure provides a 10-week period after surgery to examine very large changes in the pathology of DN. The model may be particularly useful for testing new therapies and for analysis of the progression of albuminuria and fibrosis in DN.
authors.affiliation: Department of Pediatrics, Institute for Cellular Therapeutics, University of Louisville, Louisville, KY, USA.
authors.forename: Shirong
authors.initials: S
authors.lastname: Zheng
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Teresa
authors.initials: T
authors.lastname: Chen
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Xu
authors.forename: Paul N
authors.initials: PN
authors.lastname: Epstein
mesh_terms: D000419:Albuminuria / Q000209:etiology* / Q000473:pathology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D020869:Gene Expression Profiling; D005919:Glomerular Filtration Rate; D006984:Hypertrophy / Q000209:etiology; D007668:Kidney / Q000473:pathology* / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000502:physiology; D009392:Nephrectomy