Exosomes derived from human umbilical cord mesenchymal stem cells improve myocardial repair via upregulation of Smad7

Wang,Xin‑Long; Zhao,Yuan‑Yuan; Sun,Li; Shi,Yu; Li,Zhu‑Qian; Zhao,Xiang‑Dong; Xu,Chang‑Gen; Ji,Hong‑Ge; Wang,Mei; Xu,Wen‑Rong; Zhu,Wei

doi:10.3892/ijmm.2018.3496

Exosomes derived from human umbilical cord mesenchymal stem cells improve myocardial repair via upregulation of Smad7

Authors:
- Xin‑Long Wang
- Yuan‑Yuan Zhao
- Li Sun
- Yu Shi
- Zhu‑Qian Li
- Xiang‑Dong Zhao
- Chang‑Gen Xu
- Hong‑Ge Ji
- Mei Wang
- Wen‑Rong Xu
- Wei Zhu
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Affiliations: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Clinical Laboratory, Zhenjiang Provincial Blood Center, Zhenjiang, Jiangsu 212000, P.R. China
Published online on: February 16, 2018 https://doi.org/10.3892/ijmm.2018.3496
Pages: 3063-3072

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Abstract

It has been previously reported that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC)‑exosomes exhibit cardioprotective effects on the rat acute myocardial infarction (AMI) models and cardiomyocyte hypoxia injury models in vitro, however the exact mechanisms involved require further investigation. The present study aimed to investigate the repair effects of hucMSC‑exosomes on myocardial injury via the regulation of mothers against decapentaplegic homolog 7 (Smad7) expression. Compared with sham or normoxia groups (in vivo and in vitro, respectively), western blotting demonstrated that Smad7 expression was significantly decreased in the borderline area of infraction myocardium and in H9C2(2‑1) cells following hypoxia‑induced injury. Additionally, microRNA (miR)‑125b‑5p expression was markedly increased using reverse transcription‑quantitative polymerase chain reaction, but was reversed by hucMSC‑exosomes. Trypan blue staining and lactate dehydrogenase release detection demonstrated that cell injury was significantly increased in the AMI + PBS and hypoxia group compared with in the sham and normoxia groups and was inhibited by hucMSC‑exosomes. A dual luciferase reporter gene assay confirmed that Smad7 is a target gene of miR‑125b‑5p. In addition, miR‑125b‑5p mimics promoted H9C2(2‑1) cell injury following 48 h exposure to hypoxia. Downregulation of Smad7 expression under hypoxia was increased by miR‑125b‑5p mimics compared with the mimic negative control, and hucMSC‑exosomes partially alleviated this phenomenon. In conclusion, hucMSC‑exosomes may promote Smad7 expression by inhibiting miR‑125b‑5p to increase myocardial repair. The present study may provide a potential therapeutic approach to improve myocardial repair following AMI.

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