AIMS Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear. MAIN METHODS Lipopolysaccharide (LPS)-treated Caco-2 cells and dextran sodium sulfate (DSS)-treated mice were used as model of ulcerative colitis. The levels of EZH2, angiopoietin-like 4 (ANGPTL4) and cyclic adenosine monophosphate response element-binding protein 1 (CREB1) were tested via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability and apoptosis was measured via 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide or flow cytometry. The abundances of inflammatory cytokines were examined via qRT-PCR and enzyme-linked immunosorbent assay. The association between EZH2 and ANGPTL4 was explored via chromatin immunoprecipitation. The colon damage in DSS-treated mice was investigated by colon length, histological analysis, inflammatory response and apoptosis. KEY FINDINGS LPS induced viability inhibition, inflammatory response and apoptosis in Caco-2 cells. EZH2 expression was increased but ANGPTL4 and CREB1 levels were decreased in LPS-challenged Caco-2 cells. Overexpression of ANGPTL4 or CREB1 suppressed LPS-induced damage in Caco-2 cells. EZH2 could target ANGPTL4 to mediate CREB1 expression. Inhibition of EZH2 suppressed LPS-caused injury. Moreover, knockdown of ANNGPTL4 or CREB1 attenuated the role of EZH2 inhibition. DSS caused the reduced colon length and increased inflammatory response as well as apoptosis. EZH2 expression was up-regulated but ANGPTL4 and CREB1 expression were down-regulated in DSS-treated mice. SIGNIFICANCE Inhibition of EZH2 declined LPS-induced injury in Caco-2 cells by mediating ANGPTL4 and CREB1, indicating the potential of EZH2 in treatment of ulcerative colitis.

中文翻译：

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EZH2抑制促进ANGPTL4 / CREB1抑制溃疡性结肠炎的进展。

AIMS zeste同源物2（EZH2）的增强剂与溃疡性结肠炎的发展有关。然而，EZH2在溃疡性结肠炎进展中的机制仍不清楚。主要方法脂多糖（LPS）治疗的Caco-2细胞和葡聚糖硫酸钠（DSS）治疗的小鼠被用作溃疡性结肠炎的模型。通过定量实时聚合酶链反应（qRT-PCR）和western印迹检测了EZH2，血管生成素样4（ANGPTL4）和环状腺苷单磷酸反应元件结合蛋白1（CREB1）的水平。通过3-（4，5-二甲基噻唑-2-基）-2、5-二苯基溴化四唑鎓或流式细胞仪测量细胞活力和凋亡。通过qRT-PCR和酶联免疫吸附法检测了炎性细胞因子的丰度。通过染色质免疫沉淀探索了EZH2和ANGPTL4之间的关联。通过结肠长度，组织学分析，炎症反应和细胞凋亡研究了用DSS处理的小鼠的结肠损伤。主要发现LPS在Caco-2细胞中诱导了活力抑制，炎症反应和凋亡。在LPS攻击的Caco-2细胞中，EZH2表达增加，但ANGPTL4和CREB1水平降低。ANGPTL4或CREB1的过表达抑制了LPS诱导的Caco-2细胞损伤。EZH2可以靶向ANGPTL4介导CREB1表达。抑制EZH2可抑制LPS引起的损伤。此外，敲低ANNGPTL4或CREB1减弱了EZH2抑制作用。DSS导致结肠长度减少，炎症反应增加以及细胞凋亡。在DSS处理的小鼠中，EZH2表达上调，但是ANGPTL4和CREB1表达下调。意义EZH2的抑制通过介导ANGPTL4和CREB1降低了Caco-2细胞LPS诱导的损伤，表明EZH2在治疗溃疡性结肠炎中的潜力。