Abstract: FR-PO458
BMSC-Derived miR-34b-3p Inhibits Peritoneal Fibroblast-to-Myofibroblast Transdifferentiation by Downregulating Spi-C
Session Information
- Peritoneal Dialysis: Current Topics
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 702 Dialysis: Home Dialysis and Peritoneal Dialysis
Authors
- Yu, Fang, Army Medical Center of PLA, Chongqing, Chongqing, China
- Chen, Kehong, Army Medical Center of PLA, Chongqing, Chongqing, China
- He, Yani, Army Medical Center of PLA, Chongqing, Chongqing, China
Background
Peritoneal fibrosis is the main reason for the failure of peritoneal dialysis(PD). However, there is no effective intervention. Here, we examined the role and mechanism of bone marrow mesenchymal stem cell-derived exosomes(BMSC-Exos) in regulating the differentiation of fibroblasts (FB) to myofibroblasts (MFB) in peritoneal fibrosis.
Methods
C57BL/6 mice were randomly divided into 3 groups：a control group (Saline), a peritoneal injury group (2.5% glucose peritoneal dialysate + LPS), and a peritoneal injury + BMSC-Exos group. The mice were sacrificed and the parietal peritoneum was collected after 6 weeks of modeling. The peritoneum of mice was examined by transcriptomics. The composition and function of BMSC-Exos were analyzed by miRNA sequencing.
Results
Our previous studies have confirmed that exosomes can inhibit peritoneal fibrosis. The expression level of MFB markers increased gradually with the prolongation of the peritoneal fibrosis model. BMSC-Exos treatment significantly decreased the expression of mouse peritoneal MFB markers, suggesting that exosomes can inhibit the differentiation of FB into MFB. Similarly, we further confirmed the effect of BMSC-Exos in vitro. Transcriptomic analysis results revealed that SPIC gene ranked first in the differential expression genes. The mRNA and protein levels of Spi-C were significantly increased in peritoneal injury group, while were significantly down-regulated in BMSC-Exos group. After overexpression of Spi-C in vitro, the differentiation of FB to MFB was significantly increased, and the fibrotic factor (TGF-β1) and TGF-β/WNT pathway(Smad3, β-Catenin) related to FB differentiation was significantly increased, whereas BMSC-Exos intervention could inhibit FB differentiation. miRNA sequencing and bioinformatics analysis showed that miR-34b-3p is one of the main components of BMSC-Exos, and it is the only miRNA that can specifically bind to SPIC gene sequence. In vitro, miR-34b-3p mimics could down-regulate the expression of Spi-C, and the expression of Spi-C was not affected after miR-34b-3p inhibitor intervention.The results suggested that BMSC-Exos-derived miR-34b-3p inhibited the differentiation of FB into MFB by targeting Spi-C.
Conclusion
BMSC-derived miR-34b-3p targeting Spi-C can alleviate peritoneal fibrosis by inhibiting the differentiation of subperitoneal mesothelial FB into MFB.