Class C1 decoy oligodeoxynucleotide inhibits profibrotic genes expression in rat hepatic stellate cells

Mol Med Rep. 2020 Feb;21(2):667-674. doi: 10.3892/mmr.2019.10881. Epub 2019 Dec 13.

Abstract

The aim of the present study was to investigate whether class C1 decoy oligodeoxynucleotides (ODNs) can inhibit the expression of pro‑fibrotic genes associated with rat hepatic stellate cell (HSC) activation and hepatic fibrosis. Luciferase reporter assays were performed to test the promoter activities of transforming growth factor (TGF)‑β and its downstream target genes following transfection of decoy ODNs and plasmids into HSC‑T6 cells, and western blot assays were performed to measure the protein expression of those genes following decoy ODN transfection. Class C1 decoy ODNs were confirmed to inhibit the promoter activity of TGF‑β and its downstream target genes, such as type 1 collagen (COLI)α1, tissue inhibitor of metalloproteinases (TIMP)1 and α‑smooth muscle actin by Gaussia luciferase reporter assay, and to further downregulate the expression of TGF‑β, SMAD3, COLIα1 and TIMP1 by western blotting in activated HSC‑T6 cells. In conclusion, class C1 decoy ODNs inhibited pro‑fibrotic gene expression in rat HSCS by downregulating TGF‑β signaling.

Keywords: class c1 decoy oligodeoxynucleotides; transforming growth factor-β signaling; hepatic stellate cells.

MeSH terms

  • Animals
  • Cell Line
  • Collagen Type I / metabolism
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Gene Expression Regulation* / drug effects
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / pathology*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / genetics*
  • Oligodeoxyribonucleotides / pharmacology
  • Oligodeoxyribonucleotides / therapeutic use*
  • Promoter Regions, Genetic / genetics
  • Rats
  • Smad3 Protein / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transcription Factor HES-1 / genetics
  • Transcription Factor HES-1 / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Collagen Type I
  • Hes1 protein, rat
  • Oligodeoxyribonucleotides
  • Smad3 Protein
  • Tissue Inhibitor of Metalloproteinase-1
  • Transcription Factor HES-1
  • Transforming Growth Factor beta