| Summary: | 碩士 === 國立成功大學 === 生物化學暨分子生物學研究所 === 100 === Inflammatory bowel disease (IBD) is a group of inflammatory condition of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis. It was suggested that chronic inflammation increases the risk for colon cancer. Prothymosin α (ProT) is an acid-rich non-histone nuclear protein, which is known to play an important role in proliferation, transcription, chromatin remodeling, and apoptosis. Matrix metalloproteinases (MMPs), which are zinc-dependent endopeptidases, play a major role in cell behaviors, such as cell proliferation, migration, and apoptosis. However, the regulation of MMP expression in IBD is not clear. The aim of this study is to explore the relationship between MMPs and ProT in IBD. Analysis of microarray data revealed that ProT, MMP-7, and MMP-12 were overexpressed in IBD patients. Furthermore, there were significant positive correlations between the expression levels of ProT and MMP-7 as well as ProT and MMP-12. We observed that MMPs were overexpressed in ProT homozygous transgenic mice. Using bioluminescence reporter system and immunohistochemical analysis, we found that the expression of MMP-7, MMP-12, and ProT were upregulated in the mouse IBD model induced with dextran sulfate sodium (DSS). Moreover, mice overexpressing ProT and MMP exhibited more serious IBD than the control mice. MMP-7 and MMP-12 knockout mice were resistant to DSS-induced IBD, suggesting the role of ProT, MMP-7, and MMP-12 in the development of IBD. A positive correlation between MMP and ProT expression was observed in vitro. In conclusion, our results indicate that the excess level of ProT may play an important role in the regulation of MMP-7 and MMP-12 expression in inflammatory conditions during the IBD process.
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