Removal of heparan sulfate from the glomerular basement membrane blocks protein passage.
Heparan sulfate (HS) within the glomerular basement membrane (GBM) is thought to play a major role in the charge-selective properties of the glomerular capillary wall. Recent data, however, raise questions regarding the direct role of HS in glomerular filtration. For example, in situ studies suggest that HS may prevent plasma macromolecules from clogging the GBM, keeping it in an "open" state. We evaluated this potential role of HS in vivo by studying the passage of protein through the glomerular capillary wall in the presence and absence of HS. Intravenous administration of neuraminidase removed neuraminic acid--but not HS--from the GBM, and this led to albuminuria. Concomitant removal of HS with heparinase III, confirmed by ultrastructural imaging, prevented the development of albuminuria in response to neuraminidase treatment. Taken together, these results suggest that HS keeps the GBM in an open state, facilitating passage of proteins through the glomerular capillary wall.
Wijnhoven
Tessa J M
TJ
Department of Matrix Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Lensen
Joost F M
JF
Wismans
Ronnie G P
RG
Lefeber
Dirk J
DJ
Rops
Angelique L W M M
AL
van der Vlag
Johan
J
Berden
Jo H M
JH
van den Heuvel
Lambert P W J
LP
van Kuppevelt
Toin H
TH
D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D001692:Biological Transport; D002196:Capillaries / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008854:Microscopy, Electron; D008954:Models, Biological; D009438:Neuraminic Acids / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D009438:Neuraminic Acids; D009439:Neuraminidase; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase