Vascular expression of clusterin in experimental cyclosporine nephrotoxicity

Clusterin is a widely expressed glycoprotein, which appears to be induced during tissue damage. We have examined the expression of the clusterin gene in the kidney during the development of cyclosporine (CyA)-induced nephrotoxicity in the rat using in situ hybridization histochemistry. Female Sprague-Dawley rats (170 g) were divided into experimental or control groups and were given intraperitoneal injections of CyA (25 mg/kg) or vehicle respectively for 2, 4 and 6 weeks. Kidneys from animals sacrificed at these times were fixed in 4% paraformaldehyde and embedded in paraffin. Tissue sections were hybridized using either a sense or antisense riboprobe complementary to clusterin mRNA which was labelled with 32P-UTP. Clusterin gene expression was detected in scattered tubules in kidneys from control animals. Expression of clusterin in cortical collecting ducts of CyA-treated animals was evident at 2 weeks and increased substantially at 4 and 6 weeks. Clusterin expression was also seen in afferent arterioles, the glomerular capsule and transitional epithelium of the renal pelvis of kidney sections from rats treated with CyA for 6 weeks. No labelling above background was seen at any time with the sense probe. Renin immunostaining in afferent arterioles of kidney sections from animals treated with CyA showed a marked increase after 4 and 6 weeks of CyA treatment.