Evidence for a ligand receptor system mediating the biologic effects of glycated albumin in glomerular mesangial cells.
Mesangial cells cultured with albumin modified by Amadori glucose adducts exhibit decreased proliferation in association with increased elaboration of Type IV collagen. To test the hypothesis that this modulation of mesangial cell biology is linked to ligand binding, we examined renal glomerular mesangial cells for the expression of receptors that interact with Amadori-modified albumin. Murine mesangial cells bound glycated albumin in a dose-dependent and saturable manner, displaying high and low affinity binding sites. Binding of glycated but not nonglycated albumin was inhibited by monoclonal antibodies that specifically react with albumin containing fructosyllysine groups. LDL containing Amadori glucose adducts did not compete with glycated albumin for binding. These results are consistent with ligand selectively of the binding sites for an Amadori-modified sequence within an albumin domain and suggest that a ligand receptor system mediates the effects of glycated albumin on mesangial cell proliferation and matrix production.
Wu
V Y
VY
University of Pennsylvania, Department of Biochemistry, Philadelphia.
Cohen
M P
MP
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D016650:Fluorescein-5-isothiocyanate; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D017457:Receptors, Albumin / Q000378:metabolism*; D012709:Serum Albumin / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D000093423:Glycated Serum Albumin
D000911:Antibodies, Monoclonal; D017127:Glycation End Products, Advanced; D017457:Receptors, Albumin; D012709:Serum Albumin; D016650:Fluorescein-5-isothiocyanate; D000093423:Glycated Serum Albumin