title: A role of microRNA-370 in hepatic ischaemia-reperfusion injury by targeting transforming growth factor-β receptor II.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.forename: Guogang
authors.initials: G
authors.lastname: Li
authors.forename: Chaohui
authors.initials: C
authors.lastname: Yu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shen
authors.forename: Chengfu
authors.initials: C
authors.lastname: Xu
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Feng
authors.forename: Xuequn
authors.initials: X
authors.lastname: Zhang
authors.forename: Youming
authors.initials: Y
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D019194:Ischemic Preconditioning; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; D018836:Inflammation Mediators; C000600513:MIRN370 microRNA, rat; D035683:MicroRNAs; D009841:Oligonucleotides; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: TβRII; ischaemia-reperfusion injury; liver; microRNA-370