Abstract: FR-PO588
The Protective Effect of GSTK1 on Renal Injury in Diabetic Nephropathy by Anti-Inflammatory
Session Information
- Diabetes Mellitus and Obesity: Basic - Experimental - II
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Diabetes
- 501 Diabetes Mellitus and Obesity: Basic - Experimental
Authors
- Hu, Chun, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Yang, Ming, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Gao, Peng, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Chen, Xianghui, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Han, Yachun, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Li, Li, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Xiong, Xiaofen, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Zhao, Li, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Xiao, Li, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Li, Jun, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Liu, Fuyou, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
- Sun, Lin, Departments of nephrology, Second Xiangya Hospital Central South University, ChangSha，Hunan, China
Background
Diabetic neprhropathy (DN) is one of the most serious microvascular complication in patients with diabetes mellitus. GSTK1 is a key protein which participate in adiponectin secretion and polymerization, it can also promote the expression of adiponectin. Our previous research has demonstrated that down-regulation of GSTK1 expression in the kidney of patients with DN, which consistent with decreased adiponectin levels in the serum. However, the role of GSTK1 in the development of DN is unclear.
Methods
C57BL/6 mouse were divided into four groups: normal group (control), STZ induced diabetic mouse group(STZ), overexpression GSTK1 group (GSTK1 transgenec mouse, fGSTK1) and fGSTK1 mouse with STZ iduced diabetc group (STZ fGSTK1)(n=8). In group of STZ and fGSTK1+STZ, mouse was feeding with high fat diet(HFD) for 4 weeks, and then single intraperitoneal injection of STZ 100mg/kg,continue with HFD feeding for 12 weeks.At the end of the experiment,blood and urine was collected for biochemical determination.The renal tissue was isolated and used for pathological examination，electron microscopy，DHE，IF，IHC，PCR and western blot analysis.
Results
Compared with the control group, the weight, blood sugar, blood lipid, urine protein levels, ROS were increased significantly in STZ mouse group. The pathological change were increased notable in the kidney in STZ mouse.In STZ mouse, the epithelial cell foot process effacement in kidney was seen as detected by electron microscope, in addition,both expression of GSTK1 and adiponectin were reduced compared to control(p<0.05). Furthermore, the mRNA and protein expression of NLRP3, casepase1, IL1β, IL18 and NF-kB were increased significantly in the kidney of STZ mouse compared to control(p<0.01),which accompany with the increased expression of FN, Collagen 1 and IV. All of this change were reversed partialy in fGSTK1+STZ group（p<0.01）. There was no significant difference between fGSTK1 and control groups,
Conclusion
GSTK1 decreased the weight, blood glucose, blood lipid, urine protein, ROS level,increased adiponectinthe expression and reduced pathological changes in the kidney of STZ induced mouse. GSTK1 protected renal injury and reduce fibrosis in the kideny of diabetic mouse may through up-regulated expression of adiponectin and then inhibiting NLRP3 inflammation activity pathway