Inhibitory Effect of Nuclear Factor-кB 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)-jB plays a central role in mediating the inflammation and wound-healing responses during liver fibrogenesis. However, the involvement of NF-jB 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-jB, using a decoy oligodeoxynucleotide (ODN) strategy in liver fibrosis in vitro and in vivo. NF-jB decoy ODN contains consensus binding sequences of the NF-jB-binding site. NF-jB decoy ODN effectively suppresses transforming growth factor-b1-induced EMT in AML12 murine hepatocytes. Liver fibrosis induced by CCl4 administration was suppressed by NF-jB decoy ODN. Furthermore, NF-jB decoy ODN was shown to inhibit the EMT process in fibrotic liver in vivo. This study demonstrates the feasibility of NF-jB decoy ODN treatment for preventing liver fibrosis via EMT processes