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Abstract: SA-PO127

RIP1 and RIP3 Inhibition Ameliorate Albuminuria and Renal Tubular Injury in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Tang, Xi, West China Hospital, Sichuan University, Chengdu, SICHUAN, China
  • Li, Lingzhi, West China Hospital, Sichuan University, Chengdu, SICHUAN, China
  • Ma, Liang, West China Hospital, Sichuan University, Chengdu, SICHUAN, China
  • Fu, Ping, West China Hospital of Sichuan University, Chengdu, SIChuan, China
Background


Hyperglycemia is a key factor in the development of diabetic nephropathy, which is characterized by renal tubular inflammation, apoptosis and interstitial fibrosis. Receptor interaction protein 1 (RIP1) and 3 (RIP3) plays important role in necroptosis, apoptosis, autophage and inflammation. The present study was aimed to confirm the hypothesis that RIP3 mediated high glucose-mediated renal tubular cells and that inhibition of RIP3 confer protection against this injury in type 2 diabetes.

Methods

10-week diabetic db/db mice were administrated with selective RIP1 inhibitor, necrostatin-1 (1.65 mg/kg.d, ip ), or RIP3 inhibitor, GSK2399872A (1.9mmol/kg.d , ip ) , or an equal volume of PBS , or ramipril (3 mg/kg.d, po) for a total of 8 weeks. Non-diabetic db/m mice were used as control.

Results

In db/db mice, renal tubular RIP1 and RIP3 expression was significantly stonger than db/m mice. Treatment of necrostatin-1 or GSK2399872A ameliorate albuminuria, reducing the expression of TGF-β, collagen I, fibronectin, α-SMA, and caspase 3 in diabetic kidney. The albuminuria lowering effects of GSK2399872A (820.08±98.52 mg/g) is better than that of necrostatin-1 (1058.7704±102.35 mg/g) and ramipril (1800.66±15.68 mg/g).

Conclusion

Our findings suggest a pathogenic role of overexpressed RIP1 and RIP3 in diabetic nephropathy. Inhibition of Rip1 and Rip3 ameliorates albuminuria, renal tubular apoptosis and fibrosis in type 2 diabetes.