Role of miR-19a targeting TNF-α in mediating ulcerative colitis
Role of miR-19a targeting TNF-α in mediating ulcerative colitis
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DOI：
10.3109/00365521.2013.800991
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发表时间：
2013-07-01
影响因子：
1.9
通讯作者：
Liu, Fengbin
中科院分区：
文献类型：
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作者：
Chen, Bin;She, Shifeng;Liu, Fengbin
Objective.溃疡性结肠炎（UC）是一种广泛研究的炎症性疾病，与免疫功能、伤口愈合和组织重塑相关基因的差异表达有关。据报道，microRNA在各种癌症类型中发挥作用。然而，microRNA如何调节UC的机制仍不清楚。方法.在本研究中，我们研究了miR-19 a和肿瘤坏死因子（TNF）-α在UC和葡聚糖硫酸钠（DSS）诱导的实验性结肠炎的人结肠组织中的作用。结果我们发现，在UC患者结肠组织中，miR-19 a的表达显著降低，而TNF-α的表达显著升高。此外，在DSS治疗的小鼠结肠炎中也观察到miR-19 a和TNF-α。此外，我们观察到miR-19 a直接调节TNF-alpha表达，因为miR-19 a可以抑制野生型TNF-alpha报告基因的表达，但不能抑制突变体形式的表达。应用miR-19 a抑制剂后，炎症因子TNF-α、IL-8和GM-GSF的表达显著升高。结论总之，本研究确定了DSS诱导的实验性小鼠结肠炎和人UC中miR-19 a和TNF-α的水平，并进一步证明miR-19 a可能直接调节TNF-α。这一发现可能为UC的临床治疗提供新的见解。
Objective. Ulcerative colitis (UC) is a widely studied inflammatory disease associated with differential expression of genes involved in immune function, wound healing, and tissue remodeling. MicroRNAs have been reported to play a role in various cancer types. However, the mechanism of how microRNAs regulate UC remains unclear. Methods. In the present study, we investigated the role of miR-19a and tumor necrosis factor (TNF)-alpha in human colon tissues with UC and dextran sodium sulfate (DSS)-induced experimental colitis. Results. We identified that the expression of miR-19a was significantly reduced and TNF-alpha was remarkably increased in human colon tissue with UC. Moreover, this observation of miR-19a and TNF-alpha was also occurred in DSS-treated mice colitis. Further, we observed that miR-19a directly regulated TNF-alpha expression because miR-19a can suppress the expression of wild-type TNF-alpha reporter, but not the mutant form. The expression of inflammatory factors TNF-alpha, IL-8, and GM-GSF were significantly elevated upon application of miR-19a inhibitor. Conclusion. Taken together, this study determines the levels of miR-19a and TNF-alpha in both DSS-induced experimental murine colitis and human UC and further demonstrates that miR-19a might directly regulate TNF-alpha. The findings may provide a new insight in the clinical treatment of UC.