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Evidence for the Existence of Multiple Heparan Sulfate Proteoglycans in the Human Glomerular Basement Membrane and Mesangial Matrix
Open accessAbstract
Heparan sulfate proteoglycans (HSPGs) are essential components of the glomerular basement membrane (GBM) carrying a strong anionic charge. A well-characterized extracellular HSPG is perlecan, ubiquitously expressed in basement membranes. A cDNA construct encoding domains I and II of human perlecan was expressed as a fusion protein with glutathione S-transferase. This fusion protein was used to generate monoclonal antibody 95J10. We compared the staining pattern of 95J10 with that of M215, a previously prepared mAb that recognizes HSPG isolated from human GBM. In kidney cortex, the anti-perlecan mAb 95J10 showed a strong staining of the mesangium, Bowman's capsule, the tubular basement membrane, and stained the GBM only slightly. In contrast, M215 predominantly stained the GBM in a linear fashion. Immunoelectron microscopy supported these results, showing concentrations of perlecan in some regions of the GBM, whereas the unidentified M215 antigen was homogenously distributed throughout the GBM. In other human tissues, both antibodies also produced a different staining pattern. Furthermore, a polyclonal antiserum recognizing HSPG isolated from the GBM did not recognize perlecan from EHS tumors. These results provide evidence for the presence of another HSPG in the GBM that is immunologically distinct from perlecan. The absence of perlecan splice variants in the kidney suggests that this component is encoded by a different gene than perlecan. Given its marked expression in the GBM, this component could be a determining factor in the maintenance of selective glomerular permeability.
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Metadata
- Authors
- Groffen, A. J. A., Hop, F. W. H., Trygovason, K., Dijkman, H., Assmann, K. J. M., Veerkamp, J. H., Monnens, L. A. H., & Van Den Heuvel, L. P. W. J.
- Affiliations
- Radboud University Nijmegen (NL)
- Karolinska Institutet (SE)
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 1997-07
- Volume
- 247
- Issue
- 1
- Pages
- 175-182
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W2116932337
- Cited by
- 37
- References
- 38
- Citations by year
- 2022: 1 · 2019: 2 · 2018: 1 · 2016: 3 · 2012: 3
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- VU Research Portal (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Nierstichting
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- heparan sulfate proteoglycans, glomerular basement membrane, mesangial matrix, perlecan, immunoelectron microscopy, glomerular permeability, Bowman's capsule, tubular basement membrane, splice variants, renal cortex
- MeSH terms
- Animals, Basement Membrane, Brain Chemistry, Glomerular Mesangium, Heparitin Sulfate, Heparan Sulfate, Humans, Kidney Glomerulus, Muscles, Placenta, Proteoglycans, Recombinant Fusion Proteins, Heparan Sulfate Proteoglycans, Mice
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