Cyclosporin A stimulates transcription and procollagen secretion in tubulointerstitial fibroblasts and proximal tubular cells.
The brief study described in this report was undertaken to determine whether cyclosporin A had any direct effect on the expression of tubulointerstitial procollagens in cultured renal cells. Our findings indicate that murine tubulointerstitial fibroblasts secreted significantly more procollagen type I after the addition of cyclosporin A, whereas syngeneic proximal tubular cells expressed significantly more types I and IV procollagen after cyclosporin stimulation. These increases in procollagen gene product correlated concordantly with changes in the levels of cytoplasmic mRNA with procollagen-specific cDNA probes. Transfection of these fibroblasts and proximal tubular cells with chimeric gene constructs containing enhancer/promoter elements for alpha2(I) and alpha 1(IV) procollagen linked to a chloramphenicol acetyltransferase reporter gene indicates that the stimulatory effect of cyclosporin on procollagen expression depends, at least to some extent, on an increase in transcriptional activity.
Wolf
G
G
Department of Medicine, University of Pennsylvania, Philadelphia 19104-6144.
Killen
P D
PD
Neilson
E G
EG
D000818:Animals; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts / Q000378:metabolism; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D011347:Procollagen / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D003524:Cyclosporins; D011347:Procollagen