Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
Department of Immunology and Biotechnology, University of Pécs, Pécs, Hungary.
Mediators Inflamm. 2018 Jul 22;2018:3241406. doi: 10.1155/2018/3241406. eCollection 2018.
Understanding the molecular mechanisms inducing and regulating epithelial-to-mesenchymal transition (EMT) upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of inflammatory bowel disease (IBD). The aim of this study was to determine the expression profile of TAM family receptors in an inflamed colon. For this, we used a rat model of experimental colitis and also collected samples from colons of IBD patients. Samples were taken from both inflamed and uninflamed regions of the same colon; the total RNA was isolated, and the mRNA and microRNA expressions were monitored. We have determined that AXL is highly induced in active-inflamed colon, which is accompanied with reduced expression of AXL-regulating microRNAs. In addition, the expression of genes responsible for inducing or maintaining mesenchymal phenotype, such as SNAI1, ZEB2, VIM, MMP9, and HIF1 were all significantly induced in the active-inflamed colon of IBD patients while the epithelial marker E-cadherin (CDH1) was downregulated. We also show that, , monocytic and colonic epithelial cells increase the expression of in response to LPS or TNF stimuli, respectively. In summary, we identified several interacting genes and microRNAs with mutually exclusive expression pattern in active-inflamed colon of IBD patients. Our results shed light onto a possible - and microRNA-mediated regulation influencing epithelial-to-mesenchymal transition in IBD.
了解慢性肠道炎症诱导和调节上皮-间充质转化(EMT)的分子机制对于理解炎症性肠病(IBD)的确切发病机制至关重要。本研究旨在确定 TAM 家族受体在炎症结肠中的表达谱。为此,我们使用了实验性结肠炎大鼠模型,并收集了 IBD 患者结肠的样本。从同一结肠的炎症和非炎症区域采集样本;分离总 RNA,监测 mRNA 和 microRNA 的表达。我们已经确定,AXL 在活动性炎症结肠中高度诱导,这伴随着 AXL 调节 microRNA 的表达减少。此外,诱导或维持间充质表型的基因的表达,如 SNAI1、ZEB2、VIM、MMP9 和 HIF1,在 IBD 患者的活动性炎症结肠中均显著诱导,而上皮标记物 E-钙粘蛋白(CDH1)下调。我们还表明,单核细胞和结肠上皮细胞分别响应 LPS 或 TNF 刺激增加 的表达。总之,我们在 IBD 患者的活动性炎症结肠中鉴定了几个具有相互排斥表达模式的相互作用基因和 microRNA。我们的研究结果揭示了可能存在 microRNA 介导的调节,影响 IBD 中的上皮-间充质转化。