發炎性腸道疾病 (inflammatory bowel disease, IBD) 是一種在小腸及結腸慢性發炎的病症，在臨床上主要分成克隆氏症 (Crohn's disease) 與潰瘍性結腸炎 (ulcerative colitis) 兩種，其因慢性發炎可能增加罹患結腸癌的風險。前胸腺素 (prothymosin α, ProT) 是個酸性核蛋白，在細胞增生、轉錄、染色質的重組及凋亡 (apoptosis) 扮演重要角色。基質金屬蛋白酵素 (matrix metalloproteinase, MMP) 是個需要鋅的蛋白脢，在細胞增生、爬行及凋亡扮演重要角色。然而在IBD中，尚未釐清MMP的表現如何被調控，因此本研究主要以釐清MMP與ProT在IBD中的關係。在臨床IBD病人的microarray中發現ProT、MMP-7與MMP-12都有過量表現，且具有高度正相關性，並於ProT同型合子的轉殖小鼠中發現MMP有過量表現的情況。在實驗中利用生物活體冷光 (Xenogen IVISR Spectrum Noninvasive Quantitative Molecular Imaging System) 及免疫組織化學染色得知在糊精硫酸鈉 (dextran sulfate sodium, DSS) 所誘導的IBD模式下，ProT、MMP-7與MMP-12都有過量表現。在ProT與MMP過量表現的小鼠中發現IBD症狀比對照組嚴重，而MMP-7與MMP-12基因剔除 (Knockout) 小鼠對DSS所誘發的IBD有較高的耐受性，因此得知ProT、MMP-7與MMP-12在IBD中具有影響力。在細胞實驗中發現ProT與MMP表現量具有正相關性，並得知ProT可以調控下游MMP的表現。總結實驗得知過量表現ProT可透過調控MMP-7與MMP-12的表現在IBD的病程中扮演重要角色。

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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