title: Renal tubulointerstitial fibrosis in OVE26 type 1 diabetic mice.
abstract: OBJECTIVE
  Tubulointerstitial fibrosis (TIF) is a prominent feature of progressive diabetic nephropathy. The goal of this study was to determine if hallmarks of TIF occur in the transgenic OVE26 type 1 diabetic mouse and define signaling events associated with TIF.
  
  
  METHODS
  The expression patterns of several phenotypic markers of TIF were determined in kidneys of OVE26 diabetic and control mice by immunohistochemistry and immunoblot analysis.
  
  
  RESULTS
  Pathological signatures of TIF are an accumulation of myofibroblasts and excessive deposition of extracellular matrix in the tubulointerstitium. Kidneys from OVE26 diabetic animals exhibited an increase in tubulointerstitial myofibroblast marker (alpha-smooth muscle actin), fibronectin and collagen I staining. Abundance of the pro-fibrotic cytokine TGF-beta was also enhanced in diabetic tubules. As injury involving loss of epithelial cell-cell contact promotes tissue fibrosis, we examined expression of the adhesion protein, E-cadherin. The percent of E-cadherin-stained tubules was decreased in diabetic kidneys. Prominent regulators of TGF-beta signaling, glycogen synthase kinase-3 (GSK-3) alpha and beta, were also differentially expressed.
  
  
  CONCLUSIONS
  These results indicate that TGF-beta-induced TIF occurs in OVE26 diabetic mice, providing a practical in vivo model for defining novel regulatory events and treatment strategies for diabetes-induced TIF.
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, Ky., USA. david.powell@louisville.edu
authors.forename: David W
authors.initials: DW
authors.lastname: Powell
authors.forename: Clinton C
authors.initials: CC
authors.lastname: Bertram
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Cummins
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Barati
authors.forename: Shirong
authors.initials: S
authors.lastname: Zheng
authors.forename: Paul N
authors.initials: PN
authors.lastname: Epstein
authors.forename: Jon B
authors.initials: JB
authors.lastname: Klein
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009395:Nephritis, Interstitial / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D016212:Transforming Growth Factor beta; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3