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Table of Contents
Vol. 90, No. 4, 2002
Issue release date: April 2002
Section title: Original Paper
Nephron 2002;90:460–470
(DOI:10.1159/000054735)

Sustained Expression of Thrombospondin-1 Is Associated with the Development of Glomerular and Tubulointerstitial Fibrosis in the Remnant Kidney Model

Hugo C.a · Kang D.-H.b · Johnson R.J.b
aMedizinische Klinik IV, Universität Erlangen-Nürnberg, Germany, and bDivision of Nephrology, Department of Medicine, University of Washington, Seattle, Wash., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: April 08, 2002
Issue release date: April 2002

Number of Print Pages: 11
Number of Figures: 6
Number of Tables: 0

ISSN: 1660-8151 (Print)
eISSN: 2235-3186 (Online)

For additional information: http://www.karger.com/NEF

Abstract

Background/Aims: Transforming growth factor-β1 (TGF-β1) has been implicated in the development of progressive nephrosclerosis in the remnant kidney model of chronic renal insufficiency. Thrombospondin-1 (TSP-1) is an extracellular matrix protein which has been recently shown to be capable of converting TGF-β from its latent to its active form. We studied the expression of TSP-1 mRNA and protein during the development of glomerular and tubulointerstitial nephrosclerosis in the renal ablation model particularly in relation to TGF-β1 expression. Methods: The remnant kidney model in the rat was investigated 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 7.5 weeks and 10 weeks after disease induction. Using single and double immunostaining techniques, renal tissues were examined for TSP-1 protein, TGF-β1, platelet-derived growth factor BB, extracellular matrix proteins, such as collagens and fibronectin, myofibroblast formation and macrophage influx. TSP-1 mRNA expression was investigated using a radioactive in situ hybridization technique. Results: De novo expression of TSP-1 mRNA and protein occurred in all glomerular cell types as well as in tubular cells, myofibroblasts and some macrophages in areas of tubulointerstitial injury. TSP-1 expression preceded and was sustained during the development of tubulointerstitial and glomerular fibrosis and was frequently localized at sites of increased expression of TGF-β1, but not of platelet-derived growth factor BB. Conclusion: In the remnant kidney model, the time course and localization of TSP-1 are consistent with its playing a role as a local activator of TGF-β1, thereby potentially participating in the development of nephrosclerosis.

© 2002 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: April 08, 2002
Issue release date: April 2002

Number of Print Pages: 11
Number of Figures: 6
Number of Tables: 0

ISSN: 1660-8151 (Print)
eISSN: 2235-3186 (Online)

For additional information: http://www.karger.com/NEF


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