Liver Failure and Growth
A role of microRNA-370 in hepatic ischaemia-reperfusion injury by targeting transforming growth factor-β receptor II
Article first published online: 9 JAN 2014
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 35, Issue 4, pages 1124–1132, April 2015
How to Cite
Liver Int. 2015; 35: 1124–1132
- Issue published online: 11 MAR 2015
- Article first published online: 9 JAN 2014
- Accepted manuscript online: 18 DEC 2013 10:10AM EST
- Manuscript Accepted: 11 DEC 2013
- Manuscript Received: 25 APR 2013
- Zhejiang Provincial Natural Science Foundation of China. Grant Numbers: Y2110026, LY12H03012
- Zhejiang Provincial Medical and Healthy Science Foundation of China. Grant Numbers: 2009B043, 2009A070
- Doctoral Fund of Ministry of Education of China. Grant Numbers: 20090101120110, 20110101120115
- ischaemia-reperfusion injury;
Background & Aims
MicroRNAs (miRNAs) are a group of small non-coding RNAs with modulator activity of gene expression. The role of miRNAs in hepatic ischaemia-reperfusion (IR) injury is currently largely unknown. The aim of this study was to investigate the potential role of miR-370 in hepatic IR injury.
The expression levels of hepatic miR-370 in male C57BL/6 mice subjected to hepatic IR injury or ischaemia preconditioning were assessed by quantitative real-time PCR. The effect of miR-370 on hepatic IR injury was investigated by serum enzyme analysis and histological examination of liver following treatment of mice with antagomir-370 or control. The levels of proinflammatory cytokines and apoptosis- and proliferation-related genes were also determined by quantitative real-time PCR. Furthermore, the potential targets of miR-370 in this injury were studied by bioinformatics analysis, luciferase assays, quantitative real-time PCR and Western blot.
The results showed that miR-370 expression was significantly upregulated in the mice subjected to hepatic IR injury as compared with the sham-operated mice. Inhibition of miR-370 led to the downregulation of serum aminotransferase and proinflammatory cytokines, as well as the improvement of hepatic histological damage. Reporter assays confirmed that miR-370 directly targeted the 3′ untranslated region of transforming growth factor-β receptor II (TβRII). Inhibition of miR-370 was sufficient to reinstate the expression of TβRII and its downstream target phosphorylated Smad3.
Our data suggest that miR-370 acting via TβRII might play a potential role in hepatic IR injury, and inhibition of miR-370 efficiently attenuated the damage to the liver.