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Kidney Week

Abstract: FR-PO387

Blockade of RIPK3 Alleviates Renal Fibrogenesis Through TLR2/4 Signalling in Streptozotocin-Induced Diabetic Model

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic


  • Shi, Ying, University of Sydney, Sydney, New South Wales, Australia
  • Huang, Chunling, University of Sydney, Sydney, New South Wales, Australia
  • Chen, Xinming, University of Sydney, Sydney, New South Wales, Australia
  • Pollock, Carol A., University of Sydney, Sydney, New South Wales, Australia

Current therapies for renal fibrosis are largely ineffective. Therefore, identification of novel therapeutic targets is essential. RIPK3 is identified as a crucial regulator of TLRs signalling activation, which has been well recognised to be involved in renal fibrogenesis. To date, the function of RIPK3 in renal fibrosis remains unclear.


C57BL/6 wild-type mice and C57BL/6 RIPK3 gene knock out (RIPK3-/-) mice were used in the study. streptozotocin (55 mg/kg/day) was administrated to induce diabetic model by i.p. for 5 consecutive days. After 24 weeks treatment, mice were sacrificed and urinary albumin creatinine ratio (UACR) was measured by ELISA. Kidney histological change and ECM deposition were assessed by PAS, picrosirius red staining and immunohistochemistry. Collagen IV, Fibronectin, α-SMA, TGF-β, TNF α, IL-1 β, TLR2. TLR4, MCP-1, F4/80 mRNA expression level were assessed by quantitative RT-PCR analysis.


RIPK3 deletion reduced UACR compared to the increased level of diabetic group. Both Immunohistochemical staining and PCR revealed that the absence of RIPK3 decreased the diabetic induced collagen IV and Fibronectin within kidney cortex. In addition, diabetes induced the TLR2/4 signalling activation and resulted in an increase of MCP-1 and F4/80 gene expression. However, genetic ablation of RIPK3 decreased TLR2/4 mRNA expression levels and the downstream TNF α and IL-1 β transcription associating with less MCP-1 and F4/80 gene expression. Moreover, diabetes upregulated TGF-β and α-SMA mRNA expression within kidney, whereas this effect was blocked by RIPK3 deletion.


RIPK3 is crucial in renal fibrosis by mediating TLR2/4 signalling. Our data suggest that RIPK3 blockade may be a potential novel target in renal fibrosis.


  • Government Support - Non-U.S.