Kidney Week

Abstract: SA-PO341

RIPK3 Blockade Ameliorates Renal Fibrosis in Diabetic Model of eNOS Knockout Mice

Session Information

• Mechanisms Associated with Kidney Fibrosis - II
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

• Shi, Ying, kolling institute, the University of Sydney, Sydney, New South Wales, Australia

Ying Shi,

• Zhao, Yongli, kolling institute, the University of Sydney, Sydney, Australia

Yongli Zhao,

• Huang, Chunling, kolling institute, the University of Sydney, Sydney, New South Wales, Australia

Chunling Huang,

• Chen, Xinming, kolling institute, the University of Sydney, Sydney, New South Wales, Australia

Xinming Chen,

• Pollock, Carol A., kolling institute, the University of Sydney, Sydney, New South Wales, Australia

Carol A. Pollock,

Background

Current therapies for renal fibrosis are largely ineffective. Therefore, identification of novel therapeutic targets is essential. RIPK3 is identified as a crucial regulator of necrosis, apoptosis and inflammation, which have been well recognised to be involved in renal fibrogenesis. To date, the role of RIPK3 in renal fibrosis has not been reported.

Methods

Endothelial nitric oxide synthase (eNOS) knockout mice were used in the study. STZ (55 mg/kg/day) was administrated to induce diabetic model by i.p. for 5 consecutive days. Dabrafenib (RIPK3 inhibitor) or vehicle were used as treatment on diabetic mice. After 24 weeks treatment, mice were sacrificed and kidney function was measured by 24 hour of urinary albumin excretion and urinary albumin creatinine ratio (UACR) by ELISAs. Kidney histological change and ECM deposition was assessed by PAS, Masson's trichrome, picrosirius red staining and immunohistochemistry. TGF-β expression level was detected by quantitative RT-PCR analysis.

Results

RIPK3 inhibition reduced 24 hours urinary albumin excretion and UACR compared to the increased level of vehicle diabetic group. Histological detections demonstrated the vehicle diabetic group had more renal fibrosis and ECM deposition compared to Dabrafenib treated mice. Immunohistochemistry showed consistent results on type III and type IV collagen expression on above groups. Moreover, quantitative RT-PCR exhibited Dabrafenib treated mice had lower expression level of TGF-β.

Conclusion

These results suggest that RIPK3 blockade may be a potential novel target in renal fibrosis.

Funding

• Government Support - Non-U.S.