| Summary: | 碩士 === 中國醫藥大學 === 醫學研究所碩士班 === 94 === Acetaldehyde, the very reactive intermediate of oxidative metabolism of ethanol, is potentially associated with alcohol-induced liver diseases. Matrix metalloproteinase-9 (MMP-9) is directly involved in human hepatic tumorigenesis and metastasis. However, the relationship between acetaldehyde and MMP-9 expression in liver diseases is currently poorly understood. Herein we demonstrated that acetaldehyde increased MMP-9 gelatinolytic activity and promoted cell invasion through the up-regulation of MMP-9 gene transcription in HepG2 cells. The transcription of MMP-9 gene was regulated by acetaldehyde via inductions of nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) activities. Western blot analysis indicated that acetaldehyde stimulated the translocation of NF-κB into nucleus through inhibitory κB-α (IκB-α) and c-Jun N-terminal kinase (JNK)/β-transducin repeat-containing protein (β-TrCP) signaling pathways. Acetaldehyde also induced AP-1 activity via the phosphorylation of p38 kinase. In conclusion, our findings demonstrated that acetaldehyde activated NF-κB and AP-1 activities via IκB, JNK/β-TrCP, and p38 signaling pathways, resulting in the induction of MMP-9 gene expression and the increase of cell invasion. On the basis of these data, we suggested that acetaldehyde plays an important role in tumor invasion and metastasis.
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