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      Abnormal Tenascin Expression in Murine Autosomal Recessive Polycystic Kidneys

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          Abstract

          The mechanisms responsible for renal cyst formation in congenital polycystic kidney disease (PKD) remain unknown. Changes in extracellular matrix (ECM) are regarded as an important pathogenic factor in PKD. Tenascin, an ECM glycoprotein implicated in abnormal growth in adult organs, has not been systematically evaluated in PKD. In this study, tenascin expression was studied by immunohistochemistry in the autosomal recessive polycystic kidneys of C57BL/6J (cpk/cpk) mice. Scanning electron microscopy was performed to determine the cyst types and their temporal evolution, and to establish correlations with the immunohistochemistry observations. Cystic lesions evolved in three main stages. Initially, the cysts appeared as segmental dilatations of both proximal and collecting ducts. In the second stage, the collecting duct cysts (CDCs) underwent rapid growth that led to the destruction of all other kidney elements. In the final stage, the CDCs reached their maximum size and the PKD mice died. Normal differentiated principal cells and three types of intercalated cells were present in the CDC epithelium. In all three stages an intense tenascin expression was detected selectively in the basement membranes of the cysts. In the last stage, an intense tenascin immunoreactivity was also observed in the interstitial fibrotic tissue. The abnormal presence of tenascin in the basement membranes of the cysts suggests that this glycoprotein is implicated in the pathogenesis of the cysts, possibly by stimulating cell proliferation.

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          Most cited references5

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          Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis.

          The extracellular matrix protein tenascin (previously described as myotendinous antigen) is selectively present in the mesenchyme surrounding fetal rat mammary glands, hair follicles, and teeth, three organ anlagen where the mesenchyme is essential for development. No tenascin is detectable in the normal adult mammary gland. Carcinogen-induced mammary tumors contained tenascin in their fibrous tissue. As reported for the molecule described as a "hexabrachion," tenascin contaminates so-called "cell-surface fibronectin," where it accounts for most of the detectable hemagglutinating activity. Of the extracellular matrix proteins compared, tenascin is the least effective substrate for attachment of primary mammary tumor cells, but the most effective in promoting cell growth after serum is removed from the culture medium.
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            Tenascin: an extracellular matrix protein prominent in specialized embryonic tissues and tumors.

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              Stromal-epithelial interactions in adult organs.

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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                1999
                July 1999
                21 June 1999
                : 82
                : 3
                : 261-269
                Affiliations
                Department of Anatomy and Cell Biology, University of Cantabria, Santander, Spain
                Article
                45411 Nephron 1999;82:261–269@5L}@4A}
                10.1159/000045411
                10395999
                61108eab-9833-4821-8cdb-3efd4face3b6
                © 1999 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 15, References: 46, Pages: 9
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Extracellular matrix,cpk/cpk mouse,Scanning electron microscopy,Collecting duct cysts,Tubular basement membrane

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