EFFECTS OF ALDEHYDE-MODIFIED PROTEINS ON MESANGIAL CELL-MATRIX INTERACTION

We examined the effect of aldehyde-modified matrix macromolecules on m esangial cell function in vitro, using incubated rat glomerular mesang ial cells. Laminin and fibronectin were modified by incubation for 24 h with 50 mM glycolaldehyde (GA), a highly reactive cross-linking glyc ation product, with or without equimolar aminoguanidine. GA-modified l aminin and fibronectin caused marked inhibition of cell adhesion. Cell spreading was reduced on the GA-modified laminin. In contrast, the GA -modified fibronectin had no effect on cell spreading. The study of th ymidine incorporation by mesangial cells showed that the GA-modified f ibronectin had a diminished mitogenic activity against cells. The cont ent of advanced glycation end-product (AGE), which was determined by f luorescence at 370 nm excitation and 440 nm emission wavelength, incre ased and intermolecular cross-links appeared in the GA-modified protei ns. To a large extent, aminoguanidine restored the structural alterati ons and functional deteriorations described above. We conclude that GA -modified matrix proteins diminish their functional properties against mesangial cells and affect cellular functions.