Inhibition of the Wnt/β‑catenin signaling pathway reduces autophagy levels in complement treated podocytes

Dong,Zhaocheng; Dai,Haoran; Gao,Yu; Feng,Zhendong; Liu,Wenbin; Liu,Fei; Zhang,Zihan; Ma,Fang; Xie,Xinran; Zhu,Zebing; Liu,Weijing; Liu,Baoli

doi:10.3892/etm.2021.10169

Inhibition of the Wnt/β‑catenin signaling pathway reduces autophagy levels in complement treated podocytes

Authors:
- Zhaocheng Dong
- Haoran Dai
- Yu Gao
- Zhendong Feng
- Wenbin Liu
- Fei Liu
- Zihan Zhang
- Fang Ma
- Xinran Xie
- Zebing Zhu
- Weijing Liu
- Baoli Liu
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Affiliations: Beijing University of Chinese Medicine, Chaoyang, Beijing 100029, P.R. China, Shunyi Branch, Beijing Traditional Chinese Medicine Hospital, Shunyi, Beijing 101300, P.R. China, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Dongcheng, Beijing 100010, P.R. China, Beijing Chinese Medicine Hospital, Pinggu Hospital, Pinggu, Beijing 101200, P.R. China, China Academy of Traditional Chinese Medicine, Guanganmen Hospital, Xicheng, Beijing 100053, P.R. China, Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Dongcheng, Beijing 100010, P.R. China, Key Laboratory of Chinese Internal Medicine of the Ministry of Education, Beijing University of Chinese Medicine Affiliated to Dongzhimen Hospital, Dongchen, Beijing 100700, P.R. China
Published online on: May 9, 2021 https://doi.org/10.3892/etm.2021.10169
Article Number: 737
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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