Inhibition of the Wnt/β-catenin signaling pathway reduces autophagy levels in complement treated podocytes.
Inhibition of the Wnt/β-catenin signaling pathway reduces autophagy levels in complement treated podocytes.
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DOI：
10.3892/etm.2021.10169
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发表时间：
2021-07
影响因子：
2.7
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Dong Z;Dai H;Gao Y;Feng Z;Liu W;Liu F;Zhang Z;Ma F;Xie X;Zhu Z;Liu W;Liu B
在特发性膜性肾病中，补体膜攻击复合物，更通常称为补体5b-9（C5b-9），诱导肾小球上皮细胞损伤和蛋白尿。C5b-9还可以激活许多限制或促进损伤的机制。最近的研究表明，自噬和经典的Wnt信号通路在足细胞损伤的修复中起重要作用。然而，C5b-9对这些通路的影响以及它们之间的关系仍不清楚。本研究的目的是显示C5b-9对Wnt/β-catenin信号通路和足细胞自噬的影响。采用免疫荧光染色法和毛细管免疫分析法检测相关指标的水平。C5b-9血清显著激活Wnt/β-catenin信号通路，促进自噬。用Dickkopf相关蛋白1（DKK 1）（Wnt/β-catenin通路阻断剂）处理可保护足细胞免受损伤并显著抑制自噬。结果表明，抑制Wnt/β-catenin通路生理性地激活自噬。结果表明，C5b-9导致足细胞Akt减少。然而，用DKK 1预孵育然后用C5b-9攻击的足细胞显示Akt水平增加。这可能解释了阻断Wnt/β-连环蛋白信号传导途径减弱C5b-9足细胞损伤，同时抑制自噬的观察结果。本研究的结果还表明，这两个途径的调节可能作为一种新的方法治疗特发性膜性肾病。
In idiopathic membranous nephropathy, the complement membrane attack complex, more commonly referred to as complement 5b-9 (C5b-9), induces glomerular epithelial cell injury and proteinuria. C5b-9 can also activate numerous mechanisms that restrict or facilitate injury. Recent studies suggest that autophagy and the canonical Wnt signaling pathway serve an important role in repairing podocyte injury. However, the effect of C5b-9 on these pathways and the relationship between them remains unclear. The aim of the present study was to show the effect of C5b-9 on the Wnt/β-catenin signaling pathway and autophagy in podocytes in vitro. Levels of relevant indicators were detected by immunofluorescence staining and capillary western immunoassay. C5b-9 serum significantly activated the Wnt/β-catenin signaling pathway and promoted autophagy. Treatment with Dickkopf-related protein 1 (DKK1), a Wnt/β-catenin pathway blocker, protected podocytes from injury and significantly inhibited autophagy. The results indicated that inhibition of the Wnt/β-catenin pathway physiologically activated autophagy. The results indicated that C5b-9 resulted in a decrease in Akt in podocytes. However, the podocytes preincubated with DKK1 and then attacked by C5b-9 showed an increase in Akt levels. This may explain the observation that blocking the Wnt/β-catenin signaling pathway attenuated C5b-9 podocyte damage, while inhibiting autophagy. The results of the present study also suggest that regulation of these two pathways may serve as a novel method for the treatment of idiopathic membranous nephropathy.
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影响因子：
5.4
作者：
Katoh M;Katoh M
通讯作者：
Katoh M
影响因子：
7.3
作者：
Borza DB
通讯作者：
Borza DB
影响因子：
7.3
作者：
Luo W;Olaru F;Miner JH;Beck LH Jr;van der Vlag J;Thurman JM;Borza DB
通讯作者：
Borza DB
溶酶体依赖性自噬途径的阻断导致特发性膜性肾病中补体膜攻击复合物诱导的足细胞损伤
影响因子：
4.6
作者：
Liu WJ;Li ZH;Chen XC;Zhao XL;Zhong Z;Yang C;Wu HL;An N;Li WY;Liu HF
通讯作者：
Liu HF
影响因子：
3.7
作者：
Lv, Qianying;Yang, Fengjie;Zhang, Yu
通讯作者：
Zhang, Yu