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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Podocyte Biology and the Emerging Understanding of Podocyte Diseases

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          Abstract

          The understanding of the unique molecular apparatus of the podocyte has increased dramatically in recent years. This new knowledge has improved the diagnosis and classification of the diseases that have been termed podocytopathies. Podocyte injury frequently leads to reorganization of the slit diaphragm and reorganization of the foot process structure. Four major causes of foot process effacement can be identified, with some due to genetic mutations and others due to acquired conditions: (1) impaired formation of the slit diaphragm complex; (2) abnormalities of the glomerular basement membrane or the adhesion of podocytes to the glomerular basement membrane; (3) abnormalities of the actin cytoskeleton and associated proteins, and (4) alterations in the apical membrane domain of the podocyte. The major podocytopathies can also be organized into four categories, including those with a normal glomerular histology, diffuse mesangial sclerosis, focal segmental glomerulosclerosis, and collapsing glomerulopathy.

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          Most cited references32

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          Transforming growth factor beta in tissue fibrosis.

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            NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome.

            Familial idiopathic nephrotic syndromes represent a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. A causative gene for this disease, NPHS2, was mapped to 1q25-31 and we report here its identification by positional cloning. NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier.
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              WT-1 is required for early kidney development.

              In humans, germline mutations of the WT-1 tumor suppressor gene are associated with both Wilms' tumors and urogenital malformations. To develop a model system for the molecular analysis of urogenital development, we introduced a mutation into the murine WT-1 tumor suppressor gene by gene targeting in embryonic stem cells. The mutation resulted in embryonic lethality in homozygotes, and examination of mutant embryos revealed a failure of kidney and gonad development. Specifically, at day 11 of gestation, the cells of the metanephric blastema underwent apoptosis, the ureteric bud failed to grow out from the Wolffian duct, and the inductive events that lead to formation of the metanephric kidney did not occur. In addition, the mutation caused abnormal development of the mesothelium, heart, and lungs. Our results establish a crucial role for WT-1 in early urogenital development.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2003
                October 2003
                08 September 2003
                : 23
                : 5
                : 353-360
                Affiliations
                aDepartment of Pathology, The Johns Hopkins University, Baltimore, Md., and bDivision of Nephrology, Albert Einstein College of Medicine, Bronx, N.Y., USA
                Article
                72917 Am J Nephrol 2003;23:353–360
                10.1159/000072917
                12915777
                404b441f-075e-42b2-a9ba-1749668b6362
                © 2003 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
                : 14 March 2003
                Page count
                Figures: 1, Tables: 1, References: 100, Pages: 8
                Categories
                In-Depth Topic Review

                Cardiovascular Medicine,Nephrology
                Minimal-change disease,Slit diaphragm,Focal segmental glomerulosclerosis

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