Background. Peritoneal dialysis (PD) can induce fibrosis and functional alterations in PD patients' peritoneal membranes, due to long-term unphysiological dialysate exposure, partially occurring via triggering of epithelial-to-mesenchymal transition (EMT) in peritoneal mesothelial cells (MCs). Vitamin D can ameliorate these negative effects; however, the mechanism remains unexplored. Therefore, we investigated its possible links to MCs EMT inhibition. Methods. Peritoneal fibrosis was established in Sprague-Dawley rats by chlorhexidine gluconate (CG) intraperitoneal injection for 21 days, with and without 1,25(OH)treatment. Morphological and functional evaluation and western blot analysis of EMT marker were performed upon peritoneum tissue. In vitro study was also performed in a primary human peritoneal MC culture system; MCs were incubated with transforming growth factor-β1 (TGF-β1) in the absence or presence of 1,25(OH) EMT marker expression, migration activities, and cytoskeleton redistribution of MCs were determined. Results. 1,25(OH)ameliorated CG-induced morphological and functional deterioration in animal model, along with CG-induced upregulation of -SMA and downregulation of E-cadherin expression. Meanwhile, 1,25(OH)also ameliorated TGF-β1-induced decrease in E-cadherin expression, increase in Snai1 and -SMA expression, intracellular F-actin redistribution, and migration activity in vitro. Conclusion. 1,25(OH)can ameliorate CG-induced peritoneal fibrosis and attenuate functional deterioration through inhibiting MC EMT.
All Science Journal Classification (ASJC) codes
- 免疫學與微生物學 (全部)
- 生物化學、遺傳與分子生物學 (全部)