Increases in levels of collagen types I and IV messenger ribonucleic acid in murine kidneys after treatment with ciclosporin.
We investigated changes in the levels of mRNA transcripts encoding types I and IV collagen in the kidney following the administration of ciclosporin (CS) in mice. Daily doses of CS increased the levels of mRNAs encoding collagen types I and IV in whole kidneys harvested 4 weeks after treatment. At this time point, neither a reduction of renal function detected by serum creatinine, nor histologic evidence of interstitial damage were present. Elevated levels of serum creatinine as well as mild interstitial changes did develop, however, 12 weeks after daily treatment with CS. Collagen type I transcripts were almost normal after 12 weeks, whereas levels of type IV mRNA were still elevated. Our findings indicate that increases in transcripts encoding collagens precede a deterioration in renal function and the development of interstitial changes in this murine model of chronic CS nephrotoxicity.
Wolf
G
G
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Neilson
E G
EG
D000818:Animals; D015152:Blotting, Northern; D003094:Collagen / Q000235:genetics*; D003401:Creatine / Q000097:blood; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D007668:Kidney / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D003524:Cyclosporins; D012333:RNA, Messenger; D003094:Collagen; D003401:Creatine