VASCULAR EXPRESSION OF CLUSTERIN IN EXPERIMENTAL CYCLOSPORINE NEPHROTOXICITY

Clusterin is a widely expressed glycoprotein, which appears to be indu ced during tissue damage. We have examined the expression of the clust erin gene in the kidney during the development of cyclosporine (CyA)-i nduced nephrotoxicity in the rat using in situ hybridization histochem istry. Female Sprague-Dawley rats (170 g) were divided into experiment al 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 an d embedded in paraffin. Tissue sections were hybridized using either a sense or antisense riboprobe complementary to clusterin mRNA which wa s labelled with P-32-UTP. Clusterin gene expression was detected in sc attered tubules in kidneys from control animals. Expression of cluster in in cortical collecting ducts of CyA-treated animals was evident at 2 weeks and increased substantially at 4 and 6 weeks. Clusterin expres sion was also seen in afferent arterioles, the glomerular capsule and transitional epithelium of the renal pelvis of kidney sections from ra ts treated with CyA for 6 weeks. No labelling above background was see n at any time with the sense probe. Renin immunostaining in afferent a rterioles of kidney sections from animals treated with CyA showed a ma rked increase after 4 and 6 weeks of CYA treatment.