Inhibitory effect of nuclear factor-κB decoy oligodeoxynucleotide on liver fibrosis through regulation of the epithelial-mesenchymal transition.

Abstract

The epithelial-mesenchymal transition (EMT) has been recognized to occur during embryonic development, fibrosis, and tumor metastasis. Nuclear factor (NF)-κB plays a central role in mediating the inflammation and wound-healing responses during liver fibrogenesis. However, the involvement of NF-κB during EMT in liver cells remains unidentified. To develop a therapeutic approach to EMT during liver fibrosis, we examined the inhibition of transcription factor NF-κB, using a decoy oligodeoxynucleotide (ODN) strategy in liver fibrosis in vitro and in vivo. NF-κB decoy ODN contains consensus binding sequences of the NF-κB-binding site. NF-κB decoy ODN effectively suppresses transforming growth factor-β(1)-induced EMT in AML12 murine hepatocytes. Liver fibrosis induced by CCl(4) administration was suppressed by NF-κB decoy ODN. Furthermore, NF-κB decoy ODN was shown to inhibit the EMT process in fibrotic liver in vivo. This study demonstrates the feasibility of NF-κB decoy ODN treatment for preventing liver fibrosis via EMT processes.

• Authors: Kyung-Hyun Kim, Woo-Ram Lee, Yu-Na Kang, Young-Chae Chang, Kwan-Kyu Park
• Journal: Human gene therapy (Hum Gene Ther) Vol. 25 Issue 8 Pg. 721-9 (Aug 2014) ISSN: 1557-7422 [Electronic] United States
• PMID: 24959740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Transforming Growth Factor beta1
• DNA

Topics

• Animals
• Binding Sites
• Cell Line
• DNA (administration & dosage, pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Liver Cirrhosis (drug therapy, pathology)
• Male
• Mice, Inbred C57BL
• NF-kappa B (antagonists & inhibitors, metabolism)
• Protein Binding
• Transfection
• Transforming Growth Factor beta1 (physiology)