Abnormal expression of glomerular basement membrane laminins in membranous glomerulonephritis.
BACKGROUND
Proteinuria associated with glomerular diseases is secondary to alterations of the charge-selective and/or size-selective properties of the glomerular basement membrane (GBM), but molecular alterations that are responsible for these functional changes are still poorly understood. Analysis of mice harbouring a null mutation in the gene encoding the beta 2 chain of laminin has suggested that the presence of abnormal laminin chains within the GBM can be responsible for proteinuria.


METHODS
We have investigated whether abnormal laminin ss chains could be detected by immunohistochemistry within the GBM of patients with proteinuria and minimal change disease (five patients), focal and segmental glomerulosclerosis (five patients), or primary membranous glomerulonephritis (10 patients). Three patients with mesangiocapillary glomerulonephritis and three patients with IgA nephropathy were also studied as controls.


RESULTS
We showed that the GBM of all 10 patients with membranous glomerulonephritis, but not of patients with other glomerulopathies, contained laminin beta 1, which is normally expressed only during metanephros development. The re-expression of the beta 1 chain of laminin was not associated with that of the embryonic alpha 1 chain of type IV collagen, or with the loss of expression of vimentin and synaptopodin, two markers of differentiated podocytes.


CONCLUSIONS
The presence of new laminin isoforms within the GBM of patients with membranous glomerulonephritis could play a role in the occurrence of proteinuria, by modifying either the sieving properties of the GBM or the interactions between podocytes and the GBM.
Fischer
E
E
INSERM U489, Paris VI University, Assistance Publique-Hôpitaux de Paris, Paris, France.
Mougenot
B
B
Callard
P
P
Ronco
P
P
Rossert
J
J
D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000378:metabolism* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D007797:Laminin