EARLY INCREASE OF CHONDROITIN SULFATE GLYCOSAMINOGLYCAN IN THE GLOMERULAR-BASEMENT-MEMBRANE OF RATS WITH DIABETIC GLOMERULOPATHY

A decrease in anionic change and the loss of heparan sulfate proteogly can have previously been observed in the glomerular basement membrane (GEM) during diabetic glomerulosclerosis. We studied the chronological changes in the anionic character and the glycosaminoglycan content in the GEM of WBN/Kob rats with spontaneous diabetes. Two types of catio nic probes were used: polyethyleneimine (PEI) and cationic colloidal g old (CCG). Immunogold labeling was performed with anti-monoclonal-hepa ran-sulfate-glycosaminoglycan (HS-GAG) and anti-chondroitin-sulfate-gl ycosaminoglycan (CS-GAG) antibodies. The GEM width, the anionic sites and the GAG sites were investigated in diabetic WBN/Kob rats at 2, 10 and 19 months, compared with control rats. Diabetes was confirmed in W BN/Kob rats after 8 months in this study. The GEM width gradually thic kened with age. The PEI anionic sites significantly decreased in the l amina rara externa (LRE) at 19 months (vs. 2 and 10 months). The HS-GA G sites also significantly decreased in the LRE at 10 and 19 months (v s. 2 months). However, the CCG anionic sites and the CS-GAG sites sign ificantly increased in the LRE and the lamina densa at 10 months (vs. 2 months) and, after 19 months, returned to the level seen at 2 months . Results indicate that there is an early transient increase in CS-GAG in the GEM while HS-GAG decreases. We noticed a transient increase in the CCG anionic sites at this early stage of diabetic glomerulosclero sis as well. The increase in CS-GAG may provide a marker for early dia betic changes in the GEM.