cGAS-STING activation contributes to podocyte injury in diabetic kidney disease

• DOI: 10.1016/j.isci.2022.105145
• Publication Date: 2022-09-16T04:33:10Z
• Authors: Nan Zang; Chen Cui; Xinghong Guo; Jia Song; Huiqing Hu; Mengmeng Yang; Mingyue Xu; Lingshu Wang; Xinguo Hou; Qin He; Zheng Sun; Chuan Wang; Li Chen
• Keywords: Sting; Lipotoxicity; Podocin; Nephrin

Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway activated in podocytes at early stage dysfunction, which associated with activation STING downstream effectors TBK1 and NF-κB but IRF3. Lipotoxicity induces mitochondrial damage mtDNA leakage to cytosol through Bcl-2 X protein (BAX) podocytes. BAX-mediated cytosolic can activate absence lipotoxicity sufficient podocyte injury. Depletion mtDNA, genetic knockdown, or pharmacological inhibition alleviates injury improves functions cultured mouse models diabetes obesity. These results suggest that mtDNA-cGAS-STING promotes a potential therapeutic target for other obesity-related