| dc.description.abstract | Peritoneal dialysis (PD) is a treatment option for patients with end-stage renal failure. Currently, approximately 11% of patients with renal failure worldwide are treated with PD, which causes peritoneal morphologic changes and functional deterioration. Long-term peritoneal dialysis may cause peritoneal inflammation and mesothelial-to-mesenchymal transition (MMT) of the peritoneum, and the worst case will cause encapsulated peritoneal sclerosis (EPS). It has been reported that the duration of PD treatment, the glucose concentration in the dialysate, and the occurrence of peritonitis are the major reasons cause MMT. Of note, tamoxifen has been clinically proven to be effective for a series of fibrotic diseases, such as PD-related encapsulated peritoneal sclerosis. At present, the pathogenesis of MMT caused by glucose dialysate is still not fully elucidated. From our previous study, the five candidate miRNAs showed significant fold changes between the EPS and non-EPS patients. Therefore, we dissected the functions of these candidate miRNA on peritoneal fibrosis by in vitro assays in human pleural mesothelial cells (MeT-5A).
In this study, we observed that dialysate caused time and dose-dependent toxicity in the cells, so we used TGF-β1 to induce a profibrotic phenotype in the mesothelial cells. The cellular morphology detected by cell-tracker green CMFDA dye and the fibrosis activity measured by contraction assay were changed after TGF-β1 treatments. Furthermore, the expressions of mesenchymal-related markers including N-cadherin, and vimentin were increased after TGF-β1 treatment in MeT-5A cells. Next, we investigated the effect of candidate miRNAs on peritoneal fibrosis, so we transfected candidate miRNAs into MeT-5A and added TGF-β1 for co-treatment, the results showed that TGF-β1-induced cell morphology and fibrotic phenotype could be suppressed by transfection of three individual miRNA mimics. Additionally, when miR-483-5p was overexpression, the TGF-β1-induced contraction of the gel containing mesothelial cells was attenuated. The western blot results showed that overexpression of miR-17-5p increased E-cadherin′s expression and decreased vimentin′s expression. When miR-202-3p was overexpressed, it inhibited the p-Smad2/3 protein of the TGF- β upstream signaling pathway. The results suggest that candidate miRNAs may be involved in the inhibition of mesothelial-to-mesenchymal transition, and we will further explore the potential mechanism of these candidate miRNAs in the development of peritoneal fibrosis. | en_US |