title: MicroRNA-155 attenuates activation of hepatic stellate cell by simultaneously preventing EMT process and ERK1 signalling pathway.
abstract: OBJECTIVE
  Epithelial-mesenchymal transition (EMT) process and extracellular signal-regulated kinase 1 (ERK1) signalling pathway play pivotal roles in hepatic stellate cell (HSC) activation, which is associated with the altered expression patterns of microRNAs (miRNAs). miR-155 is considered a typical multifunctional miRNA to regulate many biological processes. However, little attention has been given to the contributions of miR-155 to simultaneous regulation of EMT process and ERK1 pathway during HSC activation.
  
  
  METHODS
  Differential expression of miR-155 was assessed in activated HSC, sera and liver tissues from cirrhotic patients. Whether miR-155 could directly interact with 3'-untranslated region (3'-UTR) of T cell factor 4 (TCF4) and angiotensin II receptor type 1 (AGTR1) respectively was detected by luciferase reporter assay. The effects of enhanced miR-155 on EMT process and ERK1 pathway, cell apoptosis in HSC activation were also evaluated.
  
  
  RESULTS
  A significant decrease in miR-155 expression was observed in activated HSC, sera or liver tissues of cirrhotic patients. MiR-155 was found to simultaneously interact with 3'-UTR of TCF4 and AGTR1 mRNAs, which are known as important regulators associated with EMT and ERK1 pathway repectively. Inhibiting miR-155 expression could stimulate the EMT state and ERK1 pathway activity, thus contributing to HSC activation. Forced miR-155 expression markedly decreased the mesenchymal markers and phosphorylated ERK1 level, and enhanced E-cadherin expression, leading to the synchronous inhibitory effect on EMT and ERK1 pathway and inducing HSC apoptosis.
  
  
  CONCLUSIONS
  Our results implicate that miR-155 plays an important role in regulating the pathological network involving EMT process and ERK1 pathway during HSC activation.
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Dai
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Nan
authors.initials: N
authors.lastname: Tang
authors.forename: Xin
authors.initials: X
authors.lastname: Zeng
authors.forename: Kaiming
authors.initials: K
authors.lastname: Wu
authors.forename: Changhong
authors.initials: C
authors.lastname: Ye
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.forename: Cuihua
authors.initials: C
authors.lastname: Lu
authors.forename: Beifang
authors.initials: B
authors.lastname: Ning
authors.forename: Junping
authors.initials: J
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D055166:Hepatic Stellate Cells / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C524942:MIRN155 microRNA, human; C580597:MIRN155 microRNA, rat; D035683:MicroRNAs; D044140:Receptor, Angiotensin, Type 1; C491192:Tcf4 protein, rat; D000073940:Transcription Factor 4; D014157:Transcription Factors; D048052:Mitogen-Activated Protein Kinase 3
keywords: epithelial-mesenchymal transition (EMT); extracellular signal-regulated kinase 1 (ERK1) signalling pathway; hepatic stellate cell (HSC); microRNA-155; regulation