TY - JOUR
T1 - MiR-20a-containing exosomes from umbilical cord mesenchymal stem cells alleviates liver ischemia/reperfusion injury
AU - Zhang, Lin
AU - Song, Yaolin
AU - Chen, Lei
AU - Li, Donghang
AU - Feng, Haohao
AU - Lu, Zilong
AU - Fan, Tao
AU - Chen, Zubin
AU - Livingston, Man J.
AU - Geng, Qing
N1 - Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Mesenchymal stem cells (MSCs) have been proved to exert considerable therapeutic effects on ischemia-reperfusion (I/R)-induced injury, but the underlying mechanism remains unknown. In this study, we aimed to explore the potential molecular mechanism underlying the therapeutic effect of MSCs-derived exosome reinforced with miR-20a in reversing liver I/R injury. Quantitative real-time polymerase chain reaction, Western blot, and IHC were carried out to compare the differential expressions of miR-20a, Beclin-I, FAS, Caspase-3, mTOR and P62 in IR rats and normal rats. TUNEL was performed to assess IR-induced apoptosis in IR rats, and luciferase assay was used to confirm the inhibitory effect of miR-20a on Beclin-I and FAS expression. Among the 12 candidate microRNAs (miRNAs), miR-486, miR-25, miR-24, miR-20a,miR-466 and miR-433-3p were significantly downregulated in I/R. In particular, miR-20a, a miRNA highly expressed in umbilical cord-derived mesenchymal stem cells, was proved to bind to the 3ʹ UTR of Beclin-I and FAS to exert an inhibitory effect on their expressions. Since Beclin-I and FAS were aberrantly upregulated in IR, exosomes separated from UC-MSCs showed therapeutic efficacy in reversing I/R induced apoptosis. In addition, exosomes reinforced with miR-20a and separated from UC-MSCs almost fully alleviated I/R injury. Furthermore, our results showed that miR-20a could alleviate the abnormal expression of genes related to apoptosis and autophagy, such as active Caspase-3, mTOR, P62, and LC3II. This study presented detailed evidence to clarify the mechanism underlying the therapeutic efficacy of UC-MSCs in the treatment of I/R injury.
AB - Mesenchymal stem cells (MSCs) have been proved to exert considerable therapeutic effects on ischemia-reperfusion (I/R)-induced injury, but the underlying mechanism remains unknown. In this study, we aimed to explore the potential molecular mechanism underlying the therapeutic effect of MSCs-derived exosome reinforced with miR-20a in reversing liver I/R injury. Quantitative real-time polymerase chain reaction, Western blot, and IHC were carried out to compare the differential expressions of miR-20a, Beclin-I, FAS, Caspase-3, mTOR and P62 in IR rats and normal rats. TUNEL was performed to assess IR-induced apoptosis in IR rats, and luciferase assay was used to confirm the inhibitory effect of miR-20a on Beclin-I and FAS expression. Among the 12 candidate microRNAs (miRNAs), miR-486, miR-25, miR-24, miR-20a,miR-466 and miR-433-3p were significantly downregulated in I/R. In particular, miR-20a, a miRNA highly expressed in umbilical cord-derived mesenchymal stem cells, was proved to bind to the 3ʹ UTR of Beclin-I and FAS to exert an inhibitory effect on their expressions. Since Beclin-I and FAS were aberrantly upregulated in IR, exosomes separated from UC-MSCs showed therapeutic efficacy in reversing I/R induced apoptosis. In addition, exosomes reinforced with miR-20a and separated from UC-MSCs almost fully alleviated I/R injury. Furthermore, our results showed that miR-20a could alleviate the abnormal expression of genes related to apoptosis and autophagy, such as active Caspase-3, mTOR, P62, and LC3II. This study presented detailed evidence to clarify the mechanism underlying the therapeutic efficacy of UC-MSCs in the treatment of I/R injury.
KW - MSCs
KW - apoptosis
KW - autophagy
KW - exosome
KW - liver I/R injury
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U2 - 10.1002/jcp.29264
DO - 10.1002/jcp.29264
M3 - Article
C2 - 31566731
AN - SCOPUS:85073997712
SN - 0021-9541
VL - 235
SP - 3698
EP - 3710
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 4
ER -