Basement Membrane Defects in Genetic Kidney Diseases

The glomerular basement membrane (GBM) is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matr...

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Main Authors: Christine Chew, Rachel Lennon
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-01-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fped.2018.00011/full
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spelling doaj-1b792bfb4d284f408aa85ea011735b932020-11-24T23:22:26ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602018-01-01610.3389/fped.2018.00011318393Basement Membrane Defects in Genetic Kidney DiseasesChristine Chew0Rachel Lennon1Rachel Lennon2Faculty of Biology Medicine and Health, Wellcome Trust Centre for Cell-Matrix Research, Division of Cell Matrix Biology, School of Biological Sciences, University of Manchester, Manchester, United KingdomFaculty of Biology Medicine and Health, Wellcome Trust Centre for Cell-Matrix Research, Division of Cell Matrix Biology, School of Biological Sciences, University of Manchester, Manchester, United KingdomDepartment of Paediatric Nephrology, Royal Manchester Children’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United KingdomThe glomerular basement membrane (GBM) is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1) and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease.http://journal.frontiersin.org/article/10.3389/fped.2018.00011/fullbasement membraneglomerulusAlport syndromegenetic variationcollagen IVPierson syndrome
collection DOAJ
language English
format Article
sources DOAJ
author Christine Chew
Rachel Lennon
Rachel Lennon
spellingShingle Christine Chew
Rachel Lennon
Rachel Lennon
Basement Membrane Defects in Genetic Kidney Diseases
Frontiers in Pediatrics
basement membrane
glomerulus
Alport syndrome
genetic variation
collagen IV
Pierson syndrome
author_facet Christine Chew
Rachel Lennon
Rachel Lennon
author_sort Christine Chew
title Basement Membrane Defects in Genetic Kidney Diseases
title_short Basement Membrane Defects in Genetic Kidney Diseases
title_full Basement Membrane Defects in Genetic Kidney Diseases
title_fullStr Basement Membrane Defects in Genetic Kidney Diseases
title_full_unstemmed Basement Membrane Defects in Genetic Kidney Diseases
title_sort basement membrane defects in genetic kidney diseases
publisher Frontiers Media S.A.
series Frontiers in Pediatrics
issn 2296-2360
publishDate 2018-01-01
description The glomerular basement membrane (GBM) is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1) and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease.
topic basement membrane
glomerulus
Alport syndrome
genetic variation
collagen IV
Pierson syndrome
url http://journal.frontiersin.org/article/10.3389/fped.2018.00011/full
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