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22.02.2019 | Original Article | Ausgabe 8/2019

Digestive Diseases and Sciences 8/2019

miR-219a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury via Impairing TP53BP2

Zeitschrift:
Digestive Diseases and Sciences > Ausgabe 8/2019
Autoren:
Yu Xiao, Shouhua Zhang, Qiang Li, Zhiwen Liu, Wenli Mai, Wen Chen, Jun Lei, Huakun Hu
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10620-019-05535-4) contains supplementary material, which is available to authorized users.

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Abstract

Background

Hepatic ischemia/reperfusion (I/R) injury is a serious complication that occurs upon hypovolemic shock, liver resection, and transplantation. A significant age-dependent difference in the injury response to hepatic I/R in both human and animal models has been reported. Nevertheless, the molecular mechanism is currently unclear.

Aims

To clarify the reason why aged animals or people were more vulnerable to hepatic I/R injury.

Methods

In the present study, we found decreased miR-219a-5p expression in the old mice more vulnerable to hepatic I/R injury. Administrated with agomir-miR-219a-5p diminished the severity of hepatic I/R injury in old mice, as indicated by lower serum ALT and AST, oxidative parameters including MDA, TOA, and OSI, and decreased apoptotic cell number. The effect of miR-219a-5p was also confirmed in the H2O2-induced apoptosis model in AML-12 and NCTC1469 cells. After miR-219a-5p overexpression, two key apoptosis-related proteins Bax and P21, target genes of TP53, were decreased. Furthermore, TP53BP2 interacts with p53 family members and promotes their transcriptional activities toward pro-apoptosis genes.

Results

RNA sequencing, western blot, and luciferase reporter assay proved that TP53BP2, a crucial TP53 transcriptional activity enhancer in vivo, was directly regulated by miR-219a-5p.

Conclusions

In summary, our study demonstrated that age-related miR-219a-5p can attenuate hepatic I/R injury through inhibiting TP53BP2 and downstream TP53-dependent apoptosis of hepatic cells in mice.

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