Induction of clusterin in tubules of nephrotic rats

Clusterin is a glycoprotein induced after renal tubular cell injury. The purpose of this study was to examine the expression of clusterin in a disease model characterized early in its course by predominant glomerular injury. Male Wistar rats (weighing 251 +/- 16 g) were treated with puromycin aminonucleoside (PAN: 15 mg/100 g body wt, subcutaneously; n = 7) or vehicle (control; n = 8). The kidneys were harvested 6 d after treatment, when rats were nephrotic. Clusterin mRNA was markedly induced in the kidneys of nephrotic rats (8.5-fold versus control). Immunohistochemistry studies demonstrated clusterin primarily in tubules in the cortex and medulla. Many of the tubules staining for clusterin were dilated but had no other differentiating morphologic features. Increased numbers of proliferating tubular cells were seen at 6 d, but there was no correlation between these cells and clusterin staining. In contrast to the extent and pattern of clusterin staining, vimentin was seen in only sporadic, dilated tubules, in addition to its expected glomerular localization. An increase in clusterin mRNA was not seen 1, 2, or 4 d after PAN injection. In conclusion, tubular epithelial cell induction of clusterin occurs in the kidneys of nephrotic rats. The appearance of clusterin precedes the development of tubulointerstitial disease and may be a response to the proteinuria.