Effects of different immunosuppresants on CAN by affecting the TGF-?_1 and smads signal pathway
- VernacularTitle:免疫抑制剂对大鼠慢性移植肾肾病中转化生长因子?_1/Smads通路的影响及意义
- Author:
Rui GAO
;
Yupeng XIN
;
Yiping LU
- Publication Type:Journal Article
- Keywords:
Immunosuppressive agents;
Chronic allograft nephropathy;
Transforming growth factor beta
- From:
Chinese Journal of Organ Transplantation
2005;0(09):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of different immunosuppresants on CAN by affecting TGF-?_ 1 and Smads signal pathway. Methods The SD→Wistar rat accelerated kidney sclerosis model was made following the procedure of Kamada with our modification. The rats were divided into 6 groups (each group n=8): Group A, psudo-OP group; Group B, control group; Group C, CsA 6 mg?kg~ -1?d~ -1; Group D, FK506 0.15 mg?kg~ -1?d~ -1; Group E, MMF 20 mg?kg~ -1?d~ -1; Group F, RPM 0.8 mg?kg~ -1?d~ -1. After 4, 8, 12 weeks, the animals were killed. The immunohistochemistry and real-time fluorescence quantitative PCR were used to detect localization and expression of TGF-?_ 1, Smad2 and smad7 in transplant kidney. Results CsA and FK506 simultaneously stimulated the gene expression and protein production of TGF-?_ 1 and Smad2 and inhibited the expression of Smad7 in transplant kidney, whereas MMF and RPM could down-regulate the gene expression and protein production of TGF-?_ 1 and smad2 and up-regulate the expression of smad7. There was no significant difference between CsA group and FK506 group, as well as MMF group and RPM group.Conclusion Different immunosuppresants can affect TGF-?_ 1 and Smads signal pathway in kidney graft. CsA and FK506 can cause CAN, owning to up-regulate the expression of Smad2, and down-regulate the Smad7 expression. MMF and RPM can prevent the progression of CAN because of down-regulating the expression of Smad2 and increasing Smad7 production.
