+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Induction of α-Catenin, Integrin α3, Integrin β6, and PDGF-B by 2,8-Dihydroxyadenine Crystals in Cultured Kidney Epithelial Cells

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Background: Homozygous adenine phosphoribosyltransferase (APRT) deficiency is associated with 2,8-dihydroxyadenine (DHA) nephrolithiasis. Using whole kidney RNA from Aprt knockout mice, we previously showed that the renal deposition of DHA leads to changes in the expression of genes involved in tissue injury. To determine the cellular basis for these changes, we investigated gene expression in cultured human kidney (NHK-C) and African green monkey (BSC-1) epithelial cells exposed to DHA or calcium oxalate monohydrate (COM) crystals. Methods: First-strand cDNAs, synthesized from mRNA isolated from treated and untreated cells, were hybridized to membrane-bound cDNA arrays containing 588 genes associated with various physiological and pathological processes. Changes in gene expression were confirmed by reverse transcription PCR. Results: Twenty-seven percent of the array cDNAs were expressed in untreated NHK-C cells at varying levels relative to a housekeeping gene. The expression of three adhesion molecules (α-catenin, integrin α3, and integrin β6) and platelet-derived growth factor B (PDGF-B) was elevated following exposure of NHK-C cells to DHA. Increased expression of the adhesion molecules was also observed in BSC-1 cells, but PDGF-B expression could not be detected. COM crystals also stimulated the expression of these four genes in NHK-C cells, but the expression profile was quantitatively different compared with DHA. Conclusions: These findings suggest that DHA crystals stimulate the expression of specific genes in kidney epithelial cells and that the pathways for DHA-induced cell injury may be similar to those for COM crystals. The induction of adhesion molecules and PDGF-B may affect cell-cell or cell-matrix interactions and/or alter the actin cytoskeleton. These alterations may ultimately contribute to crystal-induced renal injury.

          Related collections

          Most cited references 13

          • Record: found
          • Abstract: found
          • Article: not found

          Computational analysis of microarray data.

          Microarray experiments are providing unprecedented quantities of genome-wide data on gene-expression patterns. Although this technique has been enthusiastically developed and applied in many biological contexts, the management and analysis of the millions of data points that result from these experiments has received less attention. Sophisticated computational tools are available, but the methods that are used to analyse the data can have a profound influence on the interpretation of the results. A basic understanding of these computational tools is therefore required for optimal experimental design and meaningful data analysis.
            • Record: found
            • Abstract: found
            • Article: not found

            PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.

            Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.
              • Record: found
              • Abstract: found
              • Article: not found

              Data management and analysis for gene expression arrays.

              Microarray technology makes it possible to simultaneously study the expression of thousands of genes during a single experiment. We have developed an information system, ArrayDB, to manage and analyse large-scale expression data. The underlying relational database was designed to allow flexibility in the nature and structure of data input and also in the generation of standard or customized reports through a web-browser interface. ArrayDB provides varied options for data retrieval and analysis tools that should facilitate the interpretation of complex hybridization results. A sampling of ArrayDB storage, retrieval and analysis capabilities is available ( ), along with information on a set of approximately 15,000 genes used to fabricate several widely used microarrays. Information stored in ArrayDB is used to provide integrated gene expression reports by linking array target sequences with NCBI's Entrez retrieval system, UniGene and KEGG pathway views. The integration of external information resources is essential in interpreting intrinsic patterns and relationships in large-scale gene expression data.

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                09 October 2002
                : 10
                : 5-6
                : 365-373
                Departments of aMedical and Molecular Genetics and bAnatomy, Indiana University School of Medicine, Indianapolis, Ind.; cDepartment of Genetics, Rutgers University, Piscataway, N.J., and dDepartment of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
                65301 Exp Nephrol 2002;10:365–373
                © 2002 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.

                Page count
                Figures: 2, Tables: 1, References: 62, Pages: 9
                Self URI (application/pdf):
                Original Paper


                Comment on this article