title: Down-regulation of miR-144 elicits proinflammatory cytokine production by targeting toll-like receptor 2 in nonalcoholic steatohepatitis of high-fat-diet-induced metabolic syndrome E3 rats.
abstract: OBJECTIVE
  To analyze regulatory microRNA(s) leading to increased TLR2 expression in livers of high-fat-diet induced metabolic syndrome (HFD-MetS) in rats with non-alcoholic steatohepatitis (NASH).
  
  
  METHODS
  TLRs, inflammatory cytokines, candidate miRNAs targeting key TLR and its cellular localization were determined in liver. The miR-144 targeting TLR2 and regulating TLR2 signaling were further determined by dual luciferase reporter assay and miR-144 mimics or inhibitor.
  
  
  RESULTS
  Expression of miR-144 was negatively correlated with TLR2 expression in Kupffer cells. The miR-144 bound to 3'UTR of rat TLR2 mRNA. In addition, compared to control group, TLR2, TNF-α, IFN-γ and activation of NF-κB decreased after miR-144 mimic challenge in NR8383 cells and BMM from E3 rats, which could be compensated by Pam3CSK4; while opposite effects on their expressions were observed after miR-144 inhibitor administration, augmented by Pam3CSK4.
  
  
  CONCLUSIONS
  Decreased miR-144 could enhance TNF-α and IFN-γ production by targeting TLR2 in vitro, and might contribute to TLR2 up-regulation and the progression of NASH in HFD-MetS E3 rats. This might offer a novel and potential target for NASH therapy.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China.
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Research Institute of Cancer, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Northwest University, Xi'an, Shaanxi 710061, China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Li
authors.affiliation: Xi'an Health School, Xi'an, Shaanxi 710054, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhong
authors.affiliation: Division of Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, SE-17177 Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Beijing, China. Electronic address: shemin.lu@gmail.com.
authors.forename: Shemin
authors.initials: S
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016207:Cytokines / Q000096:biosynthesis*; D059305:Diet, High-Fat / Q000009:adverse effects*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; C555034:MIRN144 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2
keywords: High-fat-diet induced metabolic syndrome (HFD-MetS); Kupffer cells; Nonalcoholic steatohepatitis (NASH); Proinflammatory cytokines; TLR2; miR-144