title: Conversion from cyclosporine to mycophenolate mofetil improves expression of A20 in the rat kidney allografts undergoing chronic rejection.
abstract: OBJECTIVE
  Cytoprotective genes have shown to display potent anti-inflammatory and antiapoptotic functions in endothelial and smooth muscle cells. We investigated whether cytoprotective genes, especially A20, were involved in mycophenolate mofetil (MMF)'s ability to ameliorate transplant arteriosclerosis in an experimental chronic rejection model.
  
  
  METHODS
  Sprague-Dawley rat renal grafts were orthotopically transplanted into Wistar rats following the procedure of Kamada with our modification. The recipients were divided into three oral treatment groups: (1) vehicle group (cyclosporine [CsA] 10 mg/kg.d x 10 d followed by vehicle), (2) CsA group (CsA 10 mg/kg.d x 10 d followed by CsA 6 mg/kg.d), (3) MMF group (converted from CsA 10 mg/kg.d x 10 d to MMF 20 mg/kg.d on day 11). At the same time points after transplantation, the rats were sacrificed to harvest the renal allografts. The expression of four cytoprotective genes, A20, heme oxygenase (HO)-1, Bcl-2, and Bcl-XL, was analyzed by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry.
  
  
  RESULTS
  The four-cytoprotective genes were all detected in rat kidney allografts undergoing chronic allograft nephropathy. The expression of A20 in grafted kidneys was significantly higher in the MMF than in the CsA or the vehicle group (P < .01). There was no significant difference between the CsA and the MMF groups in the expression of HO-1, Bcl-2, and Bcl-XL.
  
  
  CONCLUSIONS
  We demonstrated that MMF improved the expression of A20 in rat kidney allografts undergoing chronic allograft nephropathy. The correlation between MMF and A20 provide an explanation for the mechanism by which MMF ameliorates transplant arteriosclerosis in an experimental animal model of chronic rejection.
authors.affiliation: Transplantation Institute, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, P.R. China.
authors.forename: D
authors.initials: D
authors.lastname: Teng
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: R
authors.initials: R
authors.lastname: Gao
authors.forename: Y
authors.initials: Y
authors.lastname: Xin
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D017931:DNA Primers; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000235:genetics; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D051020:bcl-X Protein / Q000235:genetics
chemical_list: D017931:DNA Primers; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D016572:Cyclosporine; D051547:Heme Oxygenase-1; D009173:Mycophenolic Acid