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

作者：Jia, Dong; Ni, Yi-Ran; Zhang, Yan-Qiong; Rao, Chun; Hou, Jun; Tang, He-Qing; Liu, Chang-Bai^*; Wu, Jiang-Feng^*

来源：Cell and Bioscience, 2016, 6(1): 31.

DOI：10.1186/s13578-016-0094-6

• SP1 Decoy ODN
• UTE1 Decoy ODN
• TIMP1
• TGF-beta signal pathway
• Hepatic stellate cells

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, alpha-SMA and Collagen I alpha 2 (COLI alpha 2) 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-beta. 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-beta signal pathway but not the expression of TGF-beta itself.

• 出版日期2016-5-10
• 单位三峡大学