Comparison of expression of TGF-beta1, its receptors TGFbeta1R-I and TGFbeta1R-II in rat kidneys during chronic nephropathy induced by cyclosporine and tacrolimus.
OBJECTIVE
Chronic rejection is a major cause of graft dysfunction after kidney transplantation. Long-term treatment with cyclosporine (CsA) or tacrolimus (FK506) results in chronic nephrotoxicity. Transforming growth factor-beta1 (TGFbeta1) and its receptors type I (TR-I) and type II (TR-II) have been known to contribute to this side effect. The expression of TGF-beta1, TR-I, and TR-II in rat kidneys has not been compared during chronic nephropathy induced by CsA or FK506.


METHODS
Rat models of chronic CsA- or FK506-induced nephropathy were established using Sandimun Neoral or Prograf administration. The kidneys were dissected and TGF-beta1, TR-I, and TR-II proteins and TR-I and TR-II mRNAs measured by immunohistochemistry and in situ hybridization, respectively, to compare the results of the two groups.


RESULTS
The functional and morphologic studies showed that in the rats the nephrotoxic effects of FK506 were not as significant as those of CsA. The results of immunohistochemistry and in situ hybridization showed that the expression of renal TGFbeta1, TR I, TR-II proteins and TR and TR II mRNA in the FK506 group were lower than those in the CsA groups.


CONCLUSIONS
These results showed that both FK506 and CSA display nephrotoxicity, but that the nephrotoxicity of FK506 was less than that of CsA in chronic nephropathy.
Bing
P
P
Department of Surgery, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, P.R. China. Pengbing84@hotmail.com
Maode
L
L
Li
F
F
Sheng
H
H
D030201:Activin Receptors, Type I / Q000235:genetics*; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D023421:Models, Animal; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016559:Tacrolimus / Q000633:toxicity*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; D016559:Tacrolimus