Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen

Animal models have provided important insights into human renal diseases that arise from mutations in genes that encode or regulate the synthesis of glomerular basement membrane proteins. This chapter describes several well-characterized animal models of type IV collagen disorders (Alport syndrome, HANAC syndrome), a laminin disorder (Pierson syndrome), nail-patella syndrome and HERNS syndrome. These models can be exploited in studies of the pathogenesis and treatment of such disorders.

Alport syndrome

Pathogenesis

Type IV collagen

10.1159/000313956

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Citations (5)

Differential expression of laminin isoforms in diabetic nephropathy and other renal diseases

Modern Pathology (2012)

Suman Setty Alfred A Michael Alfred J. Fish S. Michael Mauer Ralph J. Butkowski

Laminin a non-collagenous glycoprotein is a major component of the renal glomerular basement membrane and mesangium. Thus far eleven distinct chains have been described, permutations of which make up 15 laminin isoforms. Laminin molecules interact with cells and other matrix molecules during organ development and differentiation. We studied the distribution of laminin isoforms in patients with type 1 diabetic nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis and IgA nephropathy/ Henoch-Schönlein purpura. Immunofluorescence microscopic studies with laminin-chain-specific antibodies to the α1, α2, α5, β1, β2 and γ1 chains detected α2, β1 and γ1 chain expression in the normal mesangium and α5, β2 and γ1 in normal glomerular basement membrane. Significantly, constituents of the glomerular basement membrane, α5, β2 and γ1 chains were overexpressed in kidneys with diabetic nephropathy. Initially the constituents of the mesangium increased commensurate with the degree of mesangial expansion and degree of diabetic nephropathy. Reduction in α2 chain intensity was observed with severe mesangial expansion and in the areas of nodular glomerulosclerosis. In addition, with late disease aberrant expression of α2 and β2 chains was observed in the mesangium. Glomerular basement membrane in renal disease overexpressed molecules normally present in that location. In summary, the alterations in basement membrane composition in various renal diseases seem to not only reflect the balance between synthesis and degradation of normal basement membrane constituents, but also their aberrant expression.

Mesangium

Membranoproliferative glomerulonephritis

Glomerular mesangium

Type IV collagen

10.1038/modpathol.2011.216

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Citations (20)

[The pulmonary-renal syndrome--the nosological and pathogenetic aspects of the problem].

PubMed (1996)

Н А Мухин

Source

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Citations (0)

[Goodpasture's syndrome. General review and report of a further case studied by immunofluorescence].

PubMed (1969)

E Tuchais M Tuchais J Pillot C Simart M Oury

Goodpasture's syndrome

Immunofluorescence

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Glomerular Basement Membrane: Molecular Structure of Type IV Collagen and Its Involvement in Diseases

Nephrology (1991)

Billy G. Hudson Sripad Gunwar Billie J. Wisdom Mark D. Hudson Milton E. Noelken

Glomerular basement membrane is a specialized extracellular matrix that functions as a molecular sieve in the nephron. Its function is altered in three notable human diseases that affect the kidneys, Goodpasture syndrome, Alport syndrome, and diabetes mellitus. Over the past decade, great advances have been made in understanding the supramolecular structure of this membrane and its role in the pathogenesis of these diseases. The membrane's major constituent is type IV collagen which provides tensile strength to the matrix and serves as a scaffold for the binding and alignment of several other macromolecular constituents. Recently, three new chains (α3, α4, and α5) of type IV collagen have been discovered, and they have been implicated in the pathogenesis of Goodpasture and Alport syndromes and potentially in that of diabetic nephropathy. This review will briefly describe the molecular structure of type IV collagen and its involvement in these diseases.

Type IV collagen

Alport syndrome

Pathogenesis

10.1007/978-3-662-35158-1_83

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Citations (0)

Glycosylation of glomerular basement membrane in type 1 (insulin-dependent) diabetic children

Diabetologia (1982)

Edith Schober Arnold Pollak H Coradello Gert Lübec

Immunoelectrophoresis

Type IV collagen

10.1007/bf00254295

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Citations (26)

Is Current Research into Basement Membrane Chemistry and Ultrastructure Providing Any New Insights into the Way the Glomerular Basement Membrane Functions?

The Nephron journals/Nephron journals (1986)

L.O. Simpson

Editorials| December 05 2008 Is Current Research into Basement Membrane Chemistry and Ultrastructure Providing Any New Insights into the Way the Glomerular Basement Membrane Functions? Subject Area: Nephrology L.O. Simpson L.O. Simpson Pathology Department, University of Otago Medical School, Dunedin, New Zealand Search for other works by this author on: This Site PubMed Google Scholar Nephron (1986) 43 (1): 1–4. https://doi.org/10.1159/000183708 Article history Published Online: December 05 2008 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation L.O. Simpson; Is Current Research into Basement Membrane Chemistry and Ultrastructure Providing Any New Insights into the Way the Glomerular Basement Membrane Functions?. Nephron 1 January 1986; 43 (1): 1–4. https://doi.org/10.1159/000183708 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsNephron Search Advanced Search This content is only available via PDF. 1986Copyright / Drug Dosage / DisclaimerCopyright: 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. Article PDF first page preview Close Modal You do not currently have access to this content.

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10.1159/000183708

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Citations (6)