Beta‐catenin participates in dialysate‐induced peritoneal fibrosis via enhanced peritoneal cell epithelial‐to‐mesenchymal transition

作者：Shuiyu Ji, Hao Deng, Wei Jin, Pengpeng Yan, Rending Wang, Lisha Pang, Jingyi Zhou, Jiaming Zhang, Xiaoying Chen, Xiang Zhao, Jia Shen · 发表于：FEBS Open Bio · 年份：2016 · DOI：10.1002/2211-5463.12182 · 被引用次数：19 · 研究领域：Wnt/β-catenin signaling in development and cancer、Tissue Engineering and Regenerative Medicine、Kruppel-like factors research

Long‐term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and thus decreases dialysis efficiency. In this study, we explored the role of β‐catenin in this process. C57BL/6 mice received daily intraperitoneal injection with 10% of the body weight of saline (control), 4.25% glucose peritoneal dialysis fluid (PDF), or PDF combined with 5 mg·kg −1 of the β‐catenin inhibitor ICG‐001 (PDF+ICG) for 30 days. Also, mice peritoneal epithelial cells (mPECs) were cultured in 4.25% glucose (HG) or combined with 10 μ m ICG‐001 (HG+ICG) for 48 h. We found greater thickness of the parietal peritoneum in the PDF‐treated mice. Additionally, lower expression of E‐cadherin, higher expression of Vimentin, β‐catenin, and Snail, and activation of β‐catenin was observed in the mice and in HG‐treated mPECs, all of which were reversed by ICG‐001. The changes in E‐cadherin and Vimentin indicated occurrence of the epithelial‐to‐mesenchymal transition (EMT). Thus, β‐catenin signaling participates in the process of HG‐induced peritoneal fibrosis, and the EMT of peritoneal epithelial cells is one of the underlying mechanisms of this pathological change.