Differential expression of basement membrane collagen chains in diabetic nephropathy.
Diabetic nephropathy is characterized by progressive expansion of mesangial matrix and thickening of the glomerular basement membrane (GBM). Kidney tissues from 13 patients with insulin-dependent diabetes mellitus were studied by immunohistochemical techniques for the distribution of three recently described collagen peptides (M28+, M28 [Good-pasture antigen], and Alport antigen) and various components of classical type IV collagen [alpha 1(IV) noncollagenous (NC) globular domain, alpha 2(IV) NC, 7S, triple helix]. Recently M28 and M28+ were designated as NC monomers of alpha 3(IV) and alpha 4(IV) based on limited amino acid sequencing. During the course of the disease, the distribution of the M28 chains and the Alport peptide segregated completely from that of classical type IV collagen. In diabetic kidneys, antibodies to the M28 and Alport peptides reacted intensely with the thickened GBM but not with the mesangium. In contrast, the reactivity of antibodies to various components of classical type IV collagen was prominent within the expanded mesangial matrix with significant decrease in reactivity in the peripheral capillary wall. In hyalinized glomeruli, components of classical type IV collagen virtually disappeared, whereas the M28 and Alport peptides persisted in the collapsed GBM. These studies support the view that expansion of the mesangial matrix and thickening of the GBM involve separate and distinct collagen components. The differential expression of the M28 and Alport peptides compared with that of classical type IV collagen may be a consequence of differing sites of synthesis (classical type IV collagen from endothelial/mesangial cells and M28 and Alport chains from visceral epithelial cells), independent control mechanisms, and/or differences in degradation.
Kim
Y
Y
Department of Pediatrics, University of Minnesota, Minneapolis 55455.
Kleppel
M M
MM
Butkowski
R
R
Mauer
S M
SM
Wieslander
J
J
Michael
A F
AF
D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000378:metabolism* / Q000648:ultrastructure; D003094:Collagen / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male
D000911:Antibodies, Monoclonal; D003094:Collagen