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

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

doi:10.1186/s13578-016-0094-6

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

Cell Biosci. 2016 May 10:6:31. doi: 10.1186/s13578-016-0094-6. eCollection 2016.

Authors

Dong Jia^#^{1

2

3}, Yi-Ran Ni^#¹, Yan-Qiong Zhang^#¹, Chun Rao^{1

2

3}, Jun Hou⁴, He-Qing Tang⁴, Chang-Bai Liu^{1

2

3}, Jiang-Feng Wu^{1

2

3}

Affiliations

¹ Medical College, China Three Gorges University, 8 Daxue Road, Xiling District, Yichang, 443002 Hubei Province China.
² Institute of Liver Diseases, China Three Gorges University, Yichang, Hubei Province China.
³ Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Hubei Province China.
⁴ First Clinical Medical College, China Three Gorges University, Yichang, Hubei Province China.

^# Contributed equally.

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.

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.

Keywords: Hepatic stellate cells; SP1 Decoy ODN; TGF-β signal pathway; TIMP1; UTE1 Decoy ODN.