Abstract: SA-PO431
Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Reduce Pericyte Transition by Inhibiting Core Fucosylation
Session Information
- Development and Regenerative Medicine
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
Authors
- Hu, Xuemei, The First Affiliated Hospital of Dalian Medical University, Dalian, LiaoNing, China
- Wang, Nan, The First Affiliated Hospital of Dalian Medical University, Dalian, LiaoNing, China
- Lin, Hong Li, The First Affiliated Hospital of Dalian Medical University, Dalian, China
Background
Renal interstitial fibrosis is the last common pathway to progression to end-stage renal disease. Myofibroblasts are a key event in renal interstitial fibrosis, and pericyte transition is one of the major sources of myofibroblasts. Our previous study found that CF (core fucosylation) mediated by FUT8 (α1,6-fucosyltransferase) could regulate the “fibrotic signaling pathway” such as TGFβ/Smad and PDGF/ERK regulate the pericytes -myofibroblasts transition in renal interstitial fibrosis.
MSCs (Mesenchymal stem cells) can alleviate renal interstitial fibrosis and are potential therapeutic targets, but the mechanism is still unclear. The exosomes are an extracellular vesicle secreted by MSCs, and can transmit functional substances such as microRNAs and proteins through membrane ligand-cell receptor interaction. It is found that exosomes could regulate damage repair, but the mechanism is also unclear.
Methods
Primary culture of pericytes to establish a TGFβ1-stimulated pericyte transition model. After cell modeling, they were co-cultured with transwell upper MSCs ,exosomes, CM, and CM for exosomes removal. Morphological changes of pericytes were observed by light microscopy. The levels of αSMA and LCA were observed by immunofluorescence. The levels of αSMA and FUT8 were observed by Western blot. The level of FUT8 was observed by HPLC (High Performance Liquid Chromatography).
Results
TGF-β1 stimulated pericytes to form spindle-shaped myofibroblasts, and the expression of αSMA, LCA and FUT8 increased, TGF-β/Smad and PDGF/ERK pathway activity increased. MSCs have an inhibitory effect, CM and exosomes have similar inhibitory effects, while CM for exosomes removal is ineffective. RT-PCR, immunofluorescence and Western blot confirmed that FUT8 was successfully transfected into pericytes. After FUT8 transfection, the degree of spindle-shaped myofibroblasts increased, and the expression of αSMA, LCA and FUT8 increased,the inhibition by MSCs，exosomes and CM was significantly weakened.
Conclusion
MSCs-derived exosomes reduce pericyte transition by inhibiting CF
Funding
- Clinical Revenue Support