Altered glomerular localization of heparan sulfate proteoglycan in experimental nephritides

The distribution of heparan sulfate proteoglycan (HS-PG) was examined electron microscopically by the high iron diamine (HID) method in puromycin aminonucleoside (PAN) nephrosis, accelerated Masugi nephritis (NTN), and serum sickness nephritis induced by bovine serum albumin (BSA nephritis) in the rat. In PAN nephrosis rats, no change was observed in the distribution of HS-PG in the lamina rara externa (LRE) of the glomerular basement membrane (GBM) throughout the experiment. In NTN rats, however, the loss of HS-PG was observed, and it was associated with subepithelial electron dense deposits formed possibly by serum sickness mechanism, but not with inflammatory cell infiltration. In BAS nephritis, immune deposits were seen in mesangial, subendothelial, intramembranous and subepithelial areas. The deposits in the former three areas seemed to have little reciprocity with the loss of HS-PG and proteinuria. Urinary protein increased in accordance with the development of subepithelial deposits and the loss of HS-PG in the area of the deposits in the LRE. These results indicate that HS-PG could be preserved even in marked proteinuric states in morphologically intact basement membrane, but altered and lost distribution of HS-PG associated with subepithelial immune deposits could in turn result in the development of proteinuria.