Exosomes derived from bone marrow mesenchymal stem cells ameliorate peritoneal fibrosis induced by high glucose peritoneal dialysate solution in mice

Abstract

Objective To investigate the role of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) in peritoneal fibrosis induced by high glucose peritoneal dialysis in mice. Methods Thirty-two male C57bl/6 mice were randomly divided into 4 groups: the normal control, the saline, the 4.25% peritoneal dialysate and the 4.25% peritoneal dialysate+exosome group. A mouse model of peritoneal fibrosis induced by high glucose peritoneal dialysis was established. The mice were sacrificed after 42 d and the specimens were collected. Peritoneal function was detected by modified peritoneal balance test (PET); The expression of peritoneal fibrosis markers was detected by immunohistochemical method; The expression of peritoneal fibrosis factor mRNA was detected by real-time quantitative PCR, and the expression of pro-fibrotic factor was detected by ELISA. Results Compared with the normal control group, the 4.25% peritoneal dialysis group had obviously increased thickness of subcutaneous area of peritoneal mesothelium (P < 0.01). The expression of peritoneal fibrosis markers (α-SMA, collagen-Ⅰ and Collagen-Ⅲ) was significantly increased in the 4.25% peritoneal dialysate group, while the expression of peritoneal fibrosis markers in the 4.25% peritoneal dialysate+exosome group was significantly lower than that in the 4.25% peritoneal dialysate group (P < 0.01). Compared with the 4.25% peritoneal dialysate+exosome group, the ultrafiltration function of mice in the 4.25% peritoneal dialysate+exosome group was significantly improved (P < 0.05). qRT-PCR results showed that the level of peritoneal fibrosis promoting factor TGF-β1 in the 4.25% peritoneal dialysate+exosome group was significantly lower than that in the 4.25% peritoneal dialysate+exosome group (P < 0.05). Conclusion Exosomes derived from BMSCs can effectively reduce peritoneal fibrosis induced by high glucose peritoneal dialysis solution in mice. Exosomes derived from BMSCs may be a new method to inhibit peritoneal fibrosis.

Keywords

• bone mesenchymal stem cells
• exosome
• peritoneal fibrosis
• peritoneal dialysis