Abstract: FR-PO0324
Podocyte RIPK3 Deletion Improves Diabetic Kidney Disease Independent of Necroptosis
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 1
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Liang, Xinling, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Li, Luan, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Zhang, Li, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Li, Jiaying, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
- Cai, Yating, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
Background
Receptor-interacting protein kinase 3 (RIPK3) is a key player in necroptosis and an emerging inflammation regulator, whose contribution to podocyte injury in diabetic kidney disease (DKD) remain unclear.
Methods
Podocyte-specific RIPK3-knockout (KO) DKD mice and high glucose (HG) cultured mouse podocytes were used to elucidate the protective effects of podocyte RIPK3 deletion on DKD，and explore the molecular pathogenic mechanisms of RIPK3 in podocyte injury. The RIPK3 kinase inhibitor GSK'872 was used to assess whether pharmacological inhibition of RIPK3 can alleviate podocyte injury in DKD.
Results
The results demonstrated that podocyte-specific RIPK3-KO alleviated albuminuria, mesangial matrix proliferation, and foot process fusion in DKD mice. In vitro, knockdown of RIPK3 using siRNA prevented podocyte injury, while knockdown of MLKL did not reverse podocyte injury induced by HG. Furthermore, knockdown of RIPK3 in vitro can alleviate HG-induced activation of the NF-κB p65-related inflammatory pathways. Importantly, GSK'872 exhibited renoprotective effects in DKD mice, indicating that RIPK3 may be a novel therapeutic target for DKD.
Conclusion
This study uncovered a novel role of podocyte RIPK3 in promoting podocyte injury and DKD progression by regulating NF-κB p65-mediated inflammatory signaling independent of necroptosis, offering novel insights for DKD management.
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