Morphological Changes in Glomerular Epithelial Cells and Basement Membranes in Puromycin Aminonucleoside Induced Nephropathy

Choi, Chan Oh; Kim, Hyun Chul; Park, Kwan Kyu

Abstract

Puromycin aminonucleoside (PAN) nephropathy was induced in a group of Sprague-Dawley rat by a single dose of intraperitoneal injection to study an ultrastructural alteration of glomerular anionic sites by stain with polyethyleneimine (PEI) as a cationic probe and to examine whether proliferation of podocytes occur by immunohistochemical stain for proliferating cell nuclear antigen (PCNA). The experimental rats developed proteinuria three days after PAN injection. Electron microscopic studies of glomeruli showed the loss of epithelial foot processes, formation of cytoplasmic vacuoles, microvillous formation and increased numbers of lyso- somes in the cytoplasm of podocytes. PEI method seems to selectively stain heparan sulfate proteogly-can in basement membrane and has been widely used to evaluate the changes of basement membrane in human disease as well as in experimental work. The anionic sites on the basement membrane with foot process fusion were mostly indistinguishable from those seen in control rats, but focal areas of loss or disarray of anionic sites were noted. The anionic sites were not seen on the basement membrane where the overlying epithelium was detached. It is strongly suggested that proteinuria in PAN nephrosis may be primarily due to a glomerular epithelial lesion, leading to focal disarray of anionic sites or focal defects in the epithelial covering of the basement membrane. The loss of anionic s'ites in the basement mernbrane may be resulted partially from the foot process fusion and mostly from the epithelial detachment. The increased numbers of PCNA positive cells after the injection of PAN is suggestive of possibility of podocytic proliferation or regeneration.