Bone marrow mesenchymal stem cells inhibit the effect of TIMP3 by transmitting miR-21-5p, thus improving the angiogenesis of rat islets
JingWen Wang1, Ying Wang1, Xiaoming Ding1, Yang Li1, Xiaohui Tian1, Xinshun Feng1, Jin Zheng1.
1Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, Shannxi Province, People's Republic of China
Purpose: Amounts of islet loss in early post-transplantation periods is a major obstacle to achieving favorable results of islet transplantation. Studies have found that bone marrow mesenchymal stem cells (BMSCs) have a protective effect on islet transplantation by promoting neovascularization, but the specific mechanism is still unclear. This study aims to investigate the effect of microRNA-21-5p, one of the important regulators of angiogenesis, on early angiogenesis induced by BMSCs and its mechanism.
Methods: After 1mg/ml collagenase P was used to digest the pancreatic tissue of SD rats, primary rat islet cells were purified by Histopaque-1077 density gradient centrifugation method, and the purity and activity of islet cells were identified by DTZ specific staining and AO-PI staining. After the original generation of islet cells and rat islet β cell line (INS-1) were cultured in BMSCs or not for 48 hours, respectively using qRT-PCR to detect microRNA-21-5p, tissue inhibitor of metalloproteinase-3 (TIMP3), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF) mRNA expression level in islet cells of co-cultured and non-co-cultured groups,and immunofluorescence and flow cytometry were used to detect islet cells activity changes.
Results: The expression of microRNA-21-5p, MMP2, MMP9, VEGF mRNA in primary islet cells and INS-1 cells co-cultured with BMSCs was significantly higher than that in the control group, and the expression of TIMP3 mRNA was significantly decreased. Compared with the non-co-culture group, the activity of islet cells after co-culture was significantly increased, and the apoptosis cells in the early stage were significantly decreased.
Conclusion: BMSCs cells can promote angiogenesis in grafts by delivering microRNA-21-5p to the islet cells, so as to improve the early ischemia and hypoxia of grafts, and ultimately improve the graft activity and survival rate.
National Nature Science Foundation of China (grant no. 81970670).. National Nature Science Foundation of China (grant no. 81970688).. Correspondence to: Dr. Xiaoming Ding,Department of Renal Transplantation,Nephropathy Hospital,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,People's Republic of China.
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