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      Characteristic Matrix and Tubular Basement Membrane Abnormalities in the CBA/Ca- kdkd Mouse Model of Hereditary Tubulointerstitial Disease

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          Abstract

          CBA/CaH- kdkd mice develop hereditary tubulointerstitial disease with mononuclear cell infiltration and cyst formation, possibly representing a model of human nephronophthisis. The purpose of the present investigation was to examine the components of the fibrotic changes which typically develop in the kidneys of these mice. By conventional histology, kdkd mice displayed progressive interstitial fibroblast and matrix accumulation. Immunohistological analysis of kdkd kidneys showed marked deposition of fibronectin in the tubulointerstitial space and revealed prominent irregularities for laminin and collagen type IV in the tubular basement membrane (TBM), including thickening, widening and folding. Electron microscopy confirmed the TBM abnormalities and showed marked undulation and thickening in areas of proximal tubular (PT) degeneration. Immunofluorescence staining analysis for the fibronectin receptors VLA-4 and VLA-5 showed no expression on injured proximal tubules, whereas the expression of the laminin receptor VLA-6 was increased and irregular on altered PT. Analysis of RNA derived from kdkd kidneys revealed marked upregulation of steady-state mRNA levels for the fibrogenic growth factor TGF-β. We conclude that TBM alterations, matrix accumulation and changes in integrin expression together with enhanced TGF-β production are typical features of kdkd tubulointerstitial disease and suggest that characteristic TBM or matrix alterations could contribute to the pathogenesis of the disease in these mice.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1998
          November 1998
          02 November 1998
          : 80
          : 3
          : 305-313
          Affiliations
          a Physiological and b Anatomical Institute, University Zürich-Irchel, and c Division of Nephrology, University Hospital, Zürich, Switzerland
          Article
          45191 Nephron 1998;80:305–313
          10.1159/000045191
          9807040
          © 1998 S. Karger AG, Basel

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          Page count
          Figures: 4, Tables: 2, References: 22, Pages: 9
          Product
          Self URI (application/pdf): https://www.karger.com/Article/Pdf/45191
          Categories
          Original Paper

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