Chen Shih-Yao, Fang Chuan-Yin, Su Bing-Hwa, Chen Hao-Ming, Huang Shih-Chi, Wu Po-Ting, Shiau Ai-Li, Wu Chao-Liang
Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 717302, Taiwan.
Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600566, Taiwan.
Biomedicines. 2024 Apr 2;12(4):780. doi: 10.3390/biomedicines12040780.
Inflammatory bowel disease (IBD) is an inflammatory condition affecting the colon and small intestine, with Crohn's disease and ulcerative colitis being the major types. Individuals with long-term IBD are at an increased risk of developing colorectal cancer. Early growth response protein 1 (Egr1) is a nuclear protein that functions as a transcriptional regulator. Egr1 is known to control the expression of numerous genes and play a role in cell growth, proliferation, and differentiation. While IBD has been associated with severe inflammation, the precise mechanisms underlying its pathogenesis remain unclear. This study aimed to investigate the role of Egr1 in the development of IBD. High levels of Egr1 expression were observed in a mouse model of colitis induced by dextran sulfate sodium (DSS), as determined by immunohistochemical (IHC) staining. Chronic DSS treatment showed that knockout (KO) mice exhibited resistance to the development of IBD, as determined by changes in their body weight and disease scores. Additionally, enzyme-linked immunosorbent assay (ELISA) and IHC staining demonstrated decreased expression levels of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α, as well as matrix metalloproteinase 12 (MMP12). Putative Egr1 binding sites were identified within the MMP12 promoter region. Through reporter assays and chromatin immunoprecipitation (ChIP) analysis, it was shown that Egr1 binds to the MMP12 promoter and regulates MMP12 expression. In conclusion, we found that Egr1 plays a role in the inflammation process of IBD through transcriptionally activating MMP12.
炎症性肠病（IBD）是一种影响结肠和小肠的炎症性疾病，主要类型为克罗恩病和溃疡性结肠炎。患有长期IBD的个体患结直肠癌的风险增加。早期生长反应蛋白1（Egr1）是一种作为转录调节因子发挥作用的核蛋白。已知Egr1可控制众多基因的表达，并在细胞生长、增殖和分化中发挥作用。虽然IBD与严重炎症有关，但其发病机制的确切原因仍不清楚。本研究旨在探讨Egr1在IBD发展中的作用。通过免疫组织化学（IHC）染色测定，在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中观察到Egr1表达水平升高。慢性DSS治疗表明，通过体重和疾病评分的变化确定，敲除（KO）小鼠对IBD的发展具有抗性。此外，酶联免疫吸附测定（ELISA）和IHC染色显示促炎细胞因子如IL-1β、IL-6和TNF-α以及基质金属蛋白酶12（MMP12）的表达水平降低。在MMP12启动子区域内鉴定出假定的Egr1结合位点。通过报告基因测定和染色质免疫沉淀（ChIP）分析表明，Egr1与MMP12启动子结合并调节MMP12的表达。总之，我们发现Egr1通过转录激活MMP12在IBD的炎症过程中发挥作用。
