Abstract: TH-PO733

Effect of GSTK1 on Ectopic Fat Deposition in the Kidney of Patients with Diabetic Nephropathy

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Chen, Xianghui, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Liu, Fuyou, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Sun, Lin, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Hu, Chun, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Zhao, Li, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Han, Yachun, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Xiong, Xiaofen, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Li, Li, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Yang, Ming, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Gao, Peng, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
  • Xiao, Li, Departments of nephrology, Second Xiangya Hospital Central South University, Changsha, China
Background

Ectopic fat deposition in kidney is closely related to the progression of diabetic nephropathy(DN). GSTK1 is a kind of protein involved in adiponectin secretion and multimerization. This study to observe by first time the relationship between the expression of GSTK1 and ectopic fat deposition(EFD) induced kidney injury in DN patients.

Methods

36 DN patients diagnosed by renal biopsy were enrolled. 30 patients with mild glomerular lesions were selected as controls. ADRP expression was used as a marker of EFD in the kidney.The expression of GSTK1 and ADRP were detected by immunohistochemistry staining. RT-PCR was used to test the GSTK1mRNA expression in PBMCs. ROS was measured by DHE staining. Lipid accumulation in kidney and cells were observed by Oil Red O staining. HK-2 cells were treated with different concentrations of glucose for 24 hours. The expression of GSTK1 and ADRP was tested by Western blot or immunofluorescence in HK-2 cell transfected with or without GSTK1 plasmid, or treated with MitoQ respectively. Mitochondrial ROS production was detected by Mitosox staining.

Results

Compared with the control group, the levels of TG, CHOL, LDL-C, BUN, SCr, UA and 24h urine protein in DN patients were incresed (p <0.05), while the HDL-C,ALB were decreased (p <0.05). The expression of GSTK1 mRNA in PBMCs was down-regulated(p<0. 01).In addition, the protein expression of GSTK1 in kidneys were decreased, while ADRP, ROS level and the deposition of lipids were significantly increased (p<0.01), which assocaited with different stages of DN. Moreover,the expression of ADRP was positively correlated with UACR, URBP and tubulointerstitial injury score ,while GSTK1 was negatively correlated with ROS level and EFD as detected by the ADRP expression and Oil red O staining in DN kidneys . In vitro study showed a notablely increased of ADRP expression,mitochondrial ROS level and intracellular lipid accumulation in HK-2 cells treated by HG or H2O2 were seen,while downregulated expression of GSTK1 protein was found. All changes above could be bloacked partially by overexpression of GSTK1 or mito Q,a target mitochondrial antioxidants,but failure to co-treatment with H2O2.

Conclusion

This data suggested that the decreased expression of GSTK1 in the kidney was significantly correlated with EFD induced renal injury in DN patients.

Funding

  • Private Foundation Support