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

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 μm 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.