Loss of heparan sulfate proteoglycan from glomerular basement membrane of nephrotic rats.

Three basement membrane components, heparan sulfate proteoglycan, laminin, and type IV collagen, were localized in renal glomeruli using light and electron microscopic immunohistochemistry in normal and aminonucleoside-treated nephrotic rats. In normal rats, type IV collagen was found in both laminae rarae and in lamina densa; laminin and heparan sulfate were found in the three layers of the basement membrane with more intense staining in both laminae rarae. In nephrotic rats laminin and type IV collagen had the same localization and distribution as in normal rats. This was in contrast to heparan sulfate proteoglycan which was lost to a considerable extent in nephrotic animals. These results support the concept that heparan sulfate proteoglycan is a major charge determinant in normal glomerular basement membrane and suggest a crucial role for this proteoglycan in the pathogenesis of the nephrotic syndrome.