Kidney Week

Abstract: FR-PO405

Inhibition of P2X7 Receptor Delays the Progression of Diabetic Nephropathy and Represses Klotho Expression

Session Information

• Diabetic Kidney Disease: Basic - II
  October 26, 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

• Higa, Elisa Mieko Suemitsu, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Elisa Mieko Suemitsu Higa,

• Fernandes, Maria jose Da silva, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Maria jose Da silva Fernandes,

• Serralha, Robson Souza, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Robson Souza Serralha,

• Lima, Deyse, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Deyse Lima,

• Punaro, Giovana, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Giovana Punaro,

• Rodrigues, Adelson, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Adelson Rodrigues,

Group or Team Name

• Laboratory of Nitric Oxide and Oxidative Stress

Background

Previous studies in our laboratory have suggested that P2X₇ could contribute to the progression of diabetic nephropathy and modulate klotho expression. Aim of this study was to investigate the role of P2X₇ knockdown in the onset of diabetic nephropathy and its possible relationship with klotho, in rats.

Methods

Seven-week-old male Wistar rats weighing 210g were all uninephrectomized; two-thirds were induced to diabetes with 60mg/kg streptozotocin i.v., and one-third received its vehicle (control rats). At 4^th day of the fifth week of the protocol, half of the diabetic rats received a small interfering RNA targeting for P2X₇ mRNA, and the other half received its vehicle. Euthanasia was made at the eighth week.

Results

Diabetic animals reproduced all classic symptoms of the disease; besides, they showed reduced renal function and low NO bioavailability; also SOD1, SOD2 and catalase were increased, probably due to the oxidative stress factors which were elevated in this situation. Metabolic data of diabetic rats did not change by silencing P2X₇ receptor. For the other hand, silencing P2X₇ was able to increase plasma and membrane forms of klotho, which in turn could have contributed to balance oxidative and nitrosative profile, ultimately improving the renal function.

Conclusion

These findings suggest that the management of P2X₇ receptor can benefit the kidneys or perhaps even other organs involved in diabetic nephropathy. Maneuvers like silencing P2X₇ can be used as an adjuvant therapy in diabetes mellitus, improving the quality of life of these patients.