title: Effects of miR-9 and tetramethylpyrazine on activation of hepatic stellate cells.
abstract: Micro-RNAs (miRNAs) are involved in regulation of the incidence and development of several hepatic diseases. Thus manipulating miRNAs may be a promising therapeutic strategy against these entities. In this study hepatic stellate cells (HSCs) were transfected with hsa-miR-9 or anti-hsa-miR-9, treated with tetramethylpyrazine (TMP), or subjected to treatment with TMP and hsa-miR-9 transfection (combined treatment group). Then, real-time polymerase chain reaction (PCR) was performed to measure mRNA levels of hsa-miR-9. Expression of hsa-miR-9 was highest in the combination treatment group compared with other groups, and significantly higher than TMP-treated and hsa-miR-9-transfected groups (both p<0.05). The anti-hsa-miR-9-transfected group expressed the lowest mRNA level of hsa-miR-9 with marked decrease versus control (p<0.05). Downstream factors that may be affected by miR-9 such as leptin, α-smooth muscle actin (SMA), and collagen I, as well as phosphorylation levels of Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) were investigated at the protein level. All these factors were regulated contrariwise to expression trends of hsa-miR-9, showing the lowest level in the combination treatment group and highest level in anti-hsa-miR-9-transfected group. These results suggest that both transfection of hsa-miR-9 and TMP can lead to upregulated endogenous expression of hsa-miR-9, inhibit activation of JAK1/STAT3 signal pathway induced by leptin, and lead to reduction of α-SMA and collagen I-thus impeding activation of HSC.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University.
authors.forename: Shan-Gao
authors.initials: SG
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Zhong
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Cao
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Hu
authors.forename: Bin
authors.initials: B
authors.lastname: Lv
mesh_terms: D000199:Actins / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D030004:Ligusticum / Q000737:chemistry; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000517:prevention & control; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000199:Actins; D024042:Collagen Type I; D020738:Leptin; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D010936:Plant Extracts; D011719:Pyrazines; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507904:JAK1 protein, human; D053613:Janus Kinase 1; C017953:tetramethylpyrazine