Abstract: SA-PO127
RIP1 and RIP3 Inhibition Ameliorate Albuminuria and Renal Tubular Injury in Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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.