A role of microRNA-370 in hepatic ischaemia-reperfusion injury by targeting transforming growth factor-β receptor II.
LIVER INTERNATIONAL(2015)
摘要
Background & AimsMicroRNAs (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. MethodsThe 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. ResultsThe 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- receptor II (TRII). Inhibition of miR-370 was sufficient to reinstate the expression of TRII and its downstream target phosphorylated Smad3. ConclusionOur data suggest that miR-370 acting via TRII might play a potential role in hepatic IR injury, and inhibition of miR-370 efficiently attenuated the damage to the liver.
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关键词
ischaemia-reperfusion injury,liver,microRNA-370,TRII
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