BACKGROUND/AIMS: 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. Copyright 2009 S. Karger AG, Basel.
BACKGROUND/AIMS: 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 diabeticmouse 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 diabeticmice, providing a practical in vivo model for defining novel regulatory events and treatment strategies for diabetes-induced TIF. Copyright 2009 S. Karger AG, Basel.
Authors: Michelle T Barati; David W Powell; Bobak D Kechavarzi; Susan M Isaacs; Shirong Zheng; Paul N Epstein; Lu Cai; Susan Coventry; Madhavi J Rane; Jon B Klein Journal: Cell Stress Chaperones Date: 2016-01 Impact factor: 3.667
Authors: Kristine A Holthouser; Amritlal Mandal; Michael L Merchant; Jeffrey R Schelling; Nicholas A Delamere; Ronald R Valdes; Suresh C Tyagi; Eleanor D Lederer; Syed J Khundmiri Journal: Am J Physiol Renal Physiol Date: 2010-04-28
Authors: Erik A Korte; Dawn J Caster; Michelle T Barati; Min Tan; Shirong Zheng; Celine C Berthier; Frank C Brosius; Mark B Vieyra; Ryan M Sheehan; Michele Kosiewicz; Marcin Wysoczynski; Patrick M Gaffney; David J Salant; Kenneth R McLeish; David W Powell Journal: Am J Pathol Date: 2017-09-19 Impact factor: 4.307
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