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.
Darby
I A
IA
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Vic., Australia.
Hewitson
T
T
Jones
C
C
Fraenkel
M B
MB
Becker
G
G
D000818:Animals; D001160:Arterioles / Q000378:metabolism; D051152:Clusterin; D016572:Cyclosporine / Q000633:toxicity*; D015342:DNA Probes; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics*; D006651:Histocytochemistry; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D007700:Kinetics; D018832:Molecular Chaperones; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000032:analysis; D016610:Tissue Embedding
D051152:Clusterin; D015342:DNA Probes; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D016572:Cyclosporine; D012083:Renin