發炎性腸道疾病(inflammatory bowel disease, IBD)是一在大腸和小腸有發炎情形的疾病，主要有克隆氏症及潰瘍性結腸炎兩種類型。研究顯示患有IBD的病人是形成大腸癌的高危險群。Early growth response-1(Egr1)是一種具有轉錄因子功能的核蛋白，而且已知EGR1會調控許多基因的表現，參與像是細胞的生長、增生以及分化。先前的研究指出IBD和嚴重的發炎情形有關。而這當中形成的致病機制卻還不是很清楚。 在這篇研究主要目的要去探討Egr1在IBD致病機轉中所扮演的角色。首先，利用免疫墨點分析法及免疫組織化學染色可以發現Egr1會大量表現在硫酸葡聚糖鈉鹽(dextran sulfate sodium, DSS)誘導的形成IBD的小鼠中。接著在長期給予低劑量的DSS，Egr1剔除小鼠可以抵擋IBD的形成。此外，酶聯免疫吸附試驗和酶譜法的使用發現到發炎前驅細胞激素interleukin-1β和interleukin-6表現量會下降，而基質金屬蛋白酶也會隨之減少。我們也在MMP12的啟動子上預測到了Egr1可能的結合位置，接著從報導基因分析和染色質免疫沉澱分析可以得出Egr1確實會結合上MMP12的啟動子也會去調控其基因的表現。從上述實驗結果我們可以得知，Egr1在IBD中會參與發炎的過程，並且會去調控發炎相關因子進一步影響IBD的產生。

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. Two major types of the disease are Crohn's disease and ulcerative colitis. People who suffer from long-term IBD are at a high risk for colorectal cancer. Early growth response-1 (Egr-1) is a nuclear protein and functions as a transcriptional regulator. It has been known that Egr-1 regulates the expression of many genes and is involved in cell growth, proliferation, and differentiation. Previous studies have shown that IBD is associated with severe inflammation. However, its exact mechanisms of disease pathogenesis remain unclear. The aim of this study way to investigate the role of Egr-1 in the pathogenesis of IBD. First, using immunoblot analysis and immunohistochemical staining, we found high levels of Egr-1 expression in the dextran sulfate sodium (DSS)-induced colitis mouse model. After chronic treatment with DSS, Egr-1 knockout mice were resistant to the development of IBD. Furthermore, enzyme-linked immunosorbent assay (ELISA) and zymographic analysis revealed that the expression levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α as well as matrix metalloproteinases (MMPs) decreased. Putative Egr-1 binding sites are present within the MMP12 promoter region. Through reporter assay and chromatin immunoprecipitation (ChIP) analysis, we demonstrated that Egr1 binds to MMP12 promoter and regulates the expression of MMP12. Based on the above data, I proposed that Egr-1 can participate in the process of inflammation and regulate other inflammation-related factors in IBD.

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