Laminin B1 is preferentially expressed in the cortex of rat kidney and is not affected by cyclosporine administration.
Cyclosporine has proven beneficial as an immunosuppressive agent for organ rejection in kidney transplants as well as in heart and liver transplants. Cyclosporine administration, however, is associated with certain adverse effects, one of the most important being chronic nephrotoxicity characterized by focal cortical scarring. Recent experimental data show involvement of type I and possibly type IV collagens in this process. Because laminin represents another potential extracellular matrix target, we examined the effects of cyclosporine administration in rats on the expression of laminin at the messenger ribonucleic acid (mRNA) and protein levels. In untreated normal rats, laminin B1 mRNA is preferentially expressed in the renal cortices, as demonstrated by northern blots. Daily administration of cyclosporine leads to focal cortical interstitial fibrosis and tubular atrophy by 4 weeks with, as shown previously, elevated procollagen alpha-1 (type I) mRNA levels at 1 and 4 weeks. In contrast, the amounts of message for laminin B1 remain identical after 1 week and 4 weeks of cyclosporine administration, despite the development of fibrosis at 4 weeks. Similar results were obtained with antilaminin antibody. We conclude that laminin is abundant in renal cortical tissues as compared with its medullary contents and is not altered in the process of renal cortical fibrosis induced by cyclosporine.
Artishevsky
A
A
Department of Medicine, Harbor-UCLA Medical Center, Torrance 90509.
Adler
S G
SG
Glassock
R J
RJ
Nast
C C
CC
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D007672:Kidney Cortex / Q000737:chemistry* / Q000187:drug effects; D007797:Laminin / Q000032:analysis* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D007797:Laminin; D012333:RNA, Messenger; D016572:Cyclosporine