Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl₄-Induced Hepatic Fibrosis Animal Model

Molecules. 2018 Aug 10;23(8):1991. doi: 10.3390/molecules23081991.

Abstract

Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to the end-stage of hepatocellular carcinoma and demolition of hepatic structures. Epithelial⁻mesenchymal transition (EMT) has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing a complementary sequence of Smad transcription factor. Thus, this study evaluated the antifibrotic effects of Smad decoy ODN on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in mice. As shown in histological results, CCl₄ treatment triggered hepatic fibrosis and increased Smad expression. On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT process. The expression of Smad signaling and EMT-associated protein was markedly decreased in Smad decoy ODN-treated mice compared with CCl₄-injured mice. In conclusion, these data indicate the practicability of Smad decoy ODN administration for preventing hepatic fibrosis and EMT processes.

Keywords: CCl4; Smad; decoy; liver fibrosis; oligodeoxynucleotide.

MeSH terms

  • Animals
  • Base Sequence
  • Carbon Tetrachloride / adverse effects
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Extracellular Matrix / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • Male
  • Mice
  • Oligodeoxyribonucleotides / chemical synthesis
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / pharmacology*
  • Signal Transduction / drug effects
  • Smad Proteins / chemistry
  • Smad Proteins / genetics*
  • Smad Proteins / metabolism
  • Transfection

Substances

  • Oligodeoxyribonucleotides
  • Smad Proteins
  • Carbon Tetrachloride