title: SP1 and UTE1 Decoy ODNs inhibit activation and proliferation of hepatic stellate cells by targeting tissue inhibitors of metalloproteinase 1.
abstract: BACKGROUND
  The excessive accumulation of extracellular matrix of hepatic fibrosis is positively correlated with tissue inhibitors of metalloproteinase 1 (TIMP1). Here we aimed to investigate whether TIMP1 may be down-regulated by Decoy ODNs strategy to capture transcriptional factor upstream TIMP1 element 1 (UTE1) and specificity protein 1(SP1).
  
  
  RESULTS
  By luciferase reporter assays, we confirmed that these Decoy ODNs could influence the promoter activation of TIMP-1, α-SMA and Collagen Iα2 (COLΙα2) genes as well as the enhancer activation of TRE in HSC-T6 cells, and the combination tended to be more effective than SP1 or UTE1 Decoy ODN alone. Western blot analysis also demonstrated down-regulation of the expression of those target genes except for TGF-β. Furthermore, we observed that the viability of HSC-T6 cells at 72 h was significantly in decline in combination group.
  
  
  CONCLUSIONS
  The combination of SP1 and UTE1 Decoy ODNs treatments inhibit the activation and proliferation of HSCs more effectively than one of the Decoy ODNs through co-regulation of TIMP1 and TGF-β signal pathway but not the expression of TGF-β itself.
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 Hubei Province China.|Institute of Liver Diseases, China Three Gorges University, Yichang, Hubei Province China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Hubei Province China.
authors.forename: Dong
authors.initials: D
authors.lastname: Jia
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 Hubei Province China.
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Ni
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 Hubei Province China.
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 Hubei Province China.|Institute of Liver Diseases, China Three Gorges University, Yichang, Hubei Province China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Hubei Province China.
authors.forename: Chun
authors.initials: C
authors.lastname: Rao
authors.affiliation: First Clinical Medical College, China Three Gorges University, Yichang, Hubei Province China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.affiliation: First Clinical Medical College, China Three Gorges University, Yichang, Hubei Province China.
authors.forename: He-Qing
authors.initials: HQ
authors.lastname: Tang
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 Hubei Province China.|Institute of Liver Diseases, China Three Gorges University, Yichang, Hubei Province China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Hubei Province China.
authors.forename: Chang-Bai
authors.initials: CB
authors.lastname: Liu
authors.affiliation: Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 Hubei Province China.|Institute of Liver Diseases, China Three Gorges University, Yichang, Hubei Province China.|Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Hubei Province China.
authors.forename: Jiang-Feng
authors.initials: JF
authors.lastname: Wu
keywords: Hepatic stellate cells; SP1 Decoy ODN; TGF-β signal pathway; TIMP1; UTE1 Decoy ODN