Abstract
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.
Highlights
Long-term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and decreases dialysis efficiency
The epithelial-to-mesenchymal transition (EMT) of peritoneal epithelial cells is considered to be one of the mechanisms underlying peritoneal fibrosis, which starts with the disruption of intercellular junctions, loss of Abbreviations epithelialto-mesenchymal transition (EMT), epithelial-to-mesenchymal transition; HG, high glucose; mPEC, mice peritoneal epithelial cell; PDF, peritoneal dialysis fluid; Peritoneal dialysis (PD), peritoneal dialysis
Immunofluorescence showed that while Vimentinpositive cells were barely seen in mPECs exposed to normal glucose (NG), they were significantly increased in those incubated in HG (Fig. 4A)
Summary
Long-term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and decreases dialysis efficiency. B-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. Long-term exposure to biologically incompatible PD fluid (PDF) containing high glucose (HG) and its metabolic products tend to interrupt the integrity of the peritoneal membrane, resulting in peritoneal fibrosis and hyperpermeability [1]. The epithelial-to-mesenchymal transition (EMT) of peritoneal epithelial cells is considered to be one of the mechanisms underlying peritoneal fibrosis, which starts with the disruption of intercellular junctions, loss of Abbreviations EMT, epithelial-to-mesenchymal transition; HG, high glucose; mPEC, mice peritoneal epithelial cell; PDF, peritoneal dialysis fluid; PD, peritoneal dialysis. The submesothelial and/or subepithelial region, which is composed of connective tissue with fibroblasts, macrophages, mast cells, and vessels, reduces the exchange efficiency and leads to functional decline [4]
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