补体 C3 通过 TLR4/NFΚB-P65 信号通路介导缺血再灌注急性肾损伤及损伤后纤维化过程中的足细胞损伤。
Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia-reperfusion acute kidney injury and post-injury fibrosis.
机构信息
Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
出版信息
Eur J Med Res. 2023 Mar 27;28(1):135. doi: 10.1186/s40001-023-01054-1.
BACKGROUND
The aim of this study was to explore the mechanism of complement C3a mediating podocyte injury during ischemia-reperfusion acute kidney injury (IR-AKI) and post-injury fibrosis.
METHODS
Renal artery clamping was used to establish IR-AKI and post-injury fibrosis model. HE and Masson staining were performed to observe renal fibrosis. The protein abundance levels were measured along with inflammatory markers, renal complement C3. Podocytes were treated with C3a with or without Toll-like receptor 4(TLR4) inhibitor. The effects of TLR4 up-regulation by TLR4 plasmids were examined.
RESULTS
C3 resulted in amelioration of renal dysfunction by reducing podocyte damage and renal fibrosis. Immunoblot with renal tissue homogenates from IR-AKI mice revealed that C3 decreased TLR4/Nuclear Factor-κB (NFκB)-P65.
CONCLUSION
Our results indicate that modulating C3/TLR4/NFκB-P65 signaling pathway is a novel therapeutic target for the IR-AKI and post-injury fibrosis.
背景
本研究旨在探讨补体 C3a 在缺血再灌注急性肾损伤（IR-AKI）及损伤后纤维化过程中介导足细胞损伤的机制。
方法
采用肾动脉夹闭法建立 IR-AKI 及损伤后纤维化模型。行 HE 和 Masson 染色观察肾纤维化。测定炎症标志物、肾补体 C3 及相关蛋白的含量。用 C3a 及其 Toll 样受体 4（TLR4）抑制剂处理足细胞，观察 TLR4 上调对其的影响。
结果
C3 通过减少足细胞损伤和肾纤维化改善肾功能障碍。IR-AKI 小鼠肾组织匀浆免疫印迹显示 C3 降低 TLR4/核因子-κB（NFκB）-P65。
结论
我们的结果表明，调节 C3/TLR4/NFκB-P65 信号通路是治疗 IR-AKI 和损伤后纤维化的新靶点。
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