Abstract: TH-PO716

Study of mTORC2 Pathway on CD4+CD25+Treg in Diabetic Nephropathy

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Li, Qiu yue, The First Affiliated Hospital of Nan Chang University, Nanchang, Jiangxi, China
  • Zhou, Jing, The first affiliated hospital of Nanchang University, Nanchang, Jiangxi, China
Background

To investigate the effect of mTORC2 pathway blocker on CD4+CD25+Treg in diabetic nephropathy (DN) rats, and to explore the possible mechanism of Treg in DN podocyte injury.

Methods

Thirty SD rats were randomly divided into DN group, DN + FK506 group and DN + ku0063794 group.Treantment groups were respectively given FK506 1mg/kg/d, ku0063794 1mg/kg/d orally every day. Blood glucose, Creatinine clearance (Ccr) and urinary protein were measured at 0, 4 , 8 weeks. The expression of mTOR, Raptor, Rictor in renal tissue was detected at 4 , 8 weeks. The levels of IL-17 and TGF-β1 in peripheral blood were detected by ELISA, and the percentage of CD4+CD25+Treg was detected by flow cytometry at 4 , 8 weeks.

Results

Urinary protein of model group was higher than control group(P<0.05), intervention groups were lower than model group (P<0.05); Ccr of model group compared with control group significantly decreased (P<0.05), intervention groups compared with model group significantly increased (P <0.05); mTOR, Raptor, Rictor increased significantly in the model group and decreased in the intervention groups (P<0.05); CD4+CD25+Treg of the model group was significantly lower than control group (P<0.05), and intervention groups were higher than model group (P<0.05); it of intervention groups at 8 week were higher than at 4 week (P<0.05); Pathological score of intervention groups compared with model group significantly decreased(P<0.05);TGF-β1 and IL-17 of the model group were significantly higher than control group (P <0.05), and the intervention groups were lower than model group (P<0.05); TGF-β1 of FK506 intervention group was lower than that of ku0063794 intervention group (P<0.05); Correlation analysis: In model group at 8 weeks, Rictor was negative correlation with CD4+ CD25=Treg and Ccr (P<0.05), positive correlation with TGF-β1,IL-17,urinary protein,pathological score (P<0.05); Raptor was positively correlated with urinary protein and pathological score (P<0.05), negative correlation with Ccr (P<0.05), no correlation with CD4+CD25+ Treg,TGF-β1,IL-17.

Conclusion

CD4+CD25+Treg may be regulated by the mTORC2 pathway in DN rats, and involved in the pathogenesis of DN.

Funding

  • Government Support - Non-U.S.