Glomerular proteoglycans in diabetic nephropathy

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The changes most characteristic of diabatic nephropathy are observed in the glomerular extracellular matrices and, include thickening of the glomerular basement membrane(GBM)and increase in the mesangial matrix. Among these, the loss of heparan sulfate proteoglycan(HS-PG)is believed to play an important role in the etiology of diabetic nephropathy. In order to clarify the role of HS-PG in diabetic nephropathy, changes in extracellular matrices was studied in renal biopsy tissues obtained from patients with diabetic nephropathy employing antibodies directed against HS-PG. By indirect immunofluorescence, a marked reduction in the intensity of staining with anti-HS-PG was observed in renal specimens from patients with nodular glomerulosclerosis and nephrotic syndrome. An increase compared to normal control sample findings in type IV collagen was observed in the mesangium of sclerosing glomeruli. By immunoelectron microscopy employing immuno-gold-gold technique, HS-PG was distributed in the lamina rara interna and externa while type IV collagen was distributed throughout the whole width of the GBM in normal controls. In diabetic patients, a loss of HS-PG both in the lamina rara interna and externa of the GBM was observed. The type IV collagen was distributed in all the layers of the thickened GBM, and the immunogold density per unit area was less as compared to the control. However, taking account for the three to five times thickening of the GBM in diabetes as compared to controls, . the absolute number of gold particles reactive with type IV collagen was increased. These findings suggest that the alterations in the concentration of immunoreactive HS-PG and type IV collagen may be relevant in the losses of charge as well as size-selectivities of the GBM, as observed in diabetic nephropathy associated with proteinuria.