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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.    Conclusion  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.

SP1 and UTE1 Decoy ODNs inhibit activation and proliferation of hepatic stellate cells by targeting tissue inhibitors of metalloproteinase 1