#4662 MSC-DERIVED EXOSOMES PREVENT PERITONEAL FIBROBLAST TRANSDIFFERENTIATION IN PERITONEAL DIALYSIS-ASSOCIATED PERITONEAL FIBROSIS

Abstract Background and Aims Peritoneal dialysis (PD) as a long-term renal replacement therapy is limited by peritoneal fibrosis. The purpose of our study was to identify the mechanism mesenchymal stem cell-derived exosomes (MSC-Exos) in regulating transdifferentiation fibroblasts (FBs) myofibroblasts (MFBs) dialysis-associated Method experimental mice were divided into 3 groups according treatment: control group (Saline), injury (2.5% glucose dialysate + LPS), exosome LPS MSC-Exos). After six weeks modeling, parietal peritoneum collected for histological analyses transcriptomic analysis. And we verified effects MSC-Exos on vitro vivo experiments referred immunofluorescence, quantitative real-time RT–PCR assay, western blotting Results First, tracing DiI-labeled showed that can enter tissue cells vitro. Our studies have found alleviate fibrosis mouse model. treatment significantly decreased expression MFBs markers (α-SMA), while maintaining phenotype (Collagen I), indicating might inhibit FBs MFBs. results further confirmed these findings. So supported could inhibiting Transcriptomic analysis revealed SPIC gene which related cell differentiation ranked first differential genes. Spi-C increased group, down-regulated group. overexpression or knockdown had no significant impact greatly with indicated be critical molecule promote differentiate mice. Moreover, miRNA sequencing miR-34b-3p one main components MSC-Exos, it specifically bind sequence. dual-luciferase reporter assay mimic reduced luciferase activity reporter. mimics down-regulate Spi-C, not affected after inhibitor intervention. above suggested MSC-Exos-derived targeting Spi-C. Conclusion subperitoneal mesothelial