sirolimus enhances cyclosporine a-induced cytotoxicity in human renal glomerular mesangial cells西罗莫司提高环孢霉素a-induced人类肾肾小球系膜细胞的细胞毒性.pdf

Hindawi Publishing Corporation Journal of Transplantation Volume 2012, Article ID 980910, 9 pages doi:10.1155/2012/980910 Research Article Sirolimus Enhances Cyclosporine A-Induced Cytotoxicity in Human Renal Glomerular Mesangial Cells ´ Sein O’Connell, Craig Slattery, Michael P. Ryan, and Tara McMorrow Renal Disease Research Group, UCD School of Biomolecular and Biomedical Research, UCD Conway Institute, University College Dublin, Dublin, Ireland Correspondence should be addressed to Tara McMorrow, tara.mcmorrow@ucd.ie Received 13 July 2011; Revised 19 September 2011; Accepted 16 October 2011 Academic Editor: Eric Thervet ´ Copyright © 2012 Sein O’Connell et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. End Stage Renal Disease (ESRD) is an ever increasing problem worldwide. However the mechanisms underlying disease progression are not fully elucidated. This work addressed nephrotoxicity induced by the immunosuppressive agents’ cyclosporine A (CsA) and sirolimus (SRL). Nephrotoxicity is the major limiting factor in long term use of CsA. SRL causes less nephrotoxicity than CsA. Therefore investigations into the differential effects of these agents may identify potential mechanisms of nephrotoxicity and means to prevent ESRD induced by therapeutic drugs. Using ELISA, Western blotting, quantitative PCR and a reporter gene assay we detailed the differential effects of CsA and SRL in human renal mesangial cells. CsA treatment increased profibrotic TGF- β 1 secretion in human mesangial cells whereas SRL did not, indicating a role for TGF-β in CsA toxicity. Howev