Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong Province, PR China.
Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong Province, PR China.
Life Sci. 2020 Jun 1;250:117553. doi: 10.1016/j.lfs.2020.117553. Epub 2020 Mar 16.
Enhancer of zeste homolog 2 (EZH2) is associated with ulcerative colitis development. However, the mechanism of EZH2 in ulcerative colitis progression remains unclear.
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.
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.
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.
EZH2 与溃疡性结肠炎的发生有关。然而，EZH2 在溃疡性结肠炎进展中的作用机制尚不清楚。
采用脂多糖（LPS）处理的 Caco-2 细胞和葡聚糖硫酸钠（DSS）处理的小鼠作为溃疡性结肠炎模型。通过实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测 EZH2、血管生成素样 4（ANGPTL4）和环磷酸腺苷反应元件结合蛋白 1（CREB1）的水平。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐或流式细胞术测定细胞活力和细胞凋亡。通过 qRT-PCR 和酶联免疫吸附试验检测炎症细胞因子的丰度。通过染色质免疫沉淀法探索 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 DSS 处理小鼠的结肠损伤。
LPS 诱导 Caco-2 细胞活力抑制、炎症反应和细胞凋亡。LPS 刺激的 Caco-2 细胞中 EZH2 表达增加，而 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 来调节 CREB1 的表达。EZH2 的抑制抑制了 LPS 引起的损伤。此外，敲低 ANNGPTL4 或 CREB1 减弱了 EZH2 抑制的作用。DSS 导致结肠长度缩短、炎症反应和细胞凋亡增加。DSS 处理的小鼠中 EZH2 表达上调，而 ANGPTL4 和 CREB1 表达下调。
EZH2 通过调节 ANGPTL4 和 CREB1 抑制 LPS 诱导的 Caco-2 细胞损伤，表明 EZH2 在治疗溃疡性结肠炎中的潜力。
