Protective Role of Coxsackie-Adenovirus Receptor in the Pathogenesis of Inflammatory Bowel Diseases.
Protective Role of Coxsackie-Adenovirus Receptor in the Pathogenesis of Inflammatory Bowel Diseases.
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柯萨奇腺病毒受体在炎症性肠病发病机制中的保护作用
DOI：
10.1155/2018/7207268
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发表时间：
2018
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Chen X;Liu R;Liu X;Xu C;Wang X
目的探讨柯萨奇-腺病毒受体（CAR）在炎症性肠病（IBD）中的作用。CAR是一种具有病毒附着功能的I型跨膜蛋白，已被证明与上皮紧密连接（TJs）相关，并介导细胞粘附，这意味着它在IBD的发病机制中可能发挥作用。方法与材料采用QPCR和Western blotting检测TNF-α诱导的NCM460、SW480细胞和IBD组织中CAD的表达，并与对照组比较，确定CAR在IBD中的作用。此外，TJs失调、fitc -葡聚糖通透性试验、qRT-PCR、Western blot和IF评估TNF-α处理的CAR过表达细胞的通透性。采用HE、qRT-PCR、Western blot和免疫组化（IHC）检测CAR过表达细胞在体内是否对DSS诱导的溃疡性结肠炎大鼠模型有治疗作用。结果发现肿瘤坏死因子α (tumor necrosis factor -α, TNF-α)能显著下调人结肠癌细胞系的CAR水平。此外，CAR的过表达可显著阻止TNF-α诱导的炎症反应、TJs失调和细胞渗透性破坏（fitc -葡聚糖渗透性测定）。与这些体外实验结果一致，我们在DSS诱导的溃疡性结肠炎大鼠模型中发现，CAR过表达可以抑制肠道炎症，减轻TJ蛋白ZO-1和Occludin的下调，并限制屏障通透性的诱导。总之，我们的研究结果强烈表明，在IBD发病过程中，CAR可以保护紧密连接并具有抗炎作用。因此，CAR可以作为诊断和治疗IBD的治疗靶点。
Aim To investigate the role of Coxsackie-adenovirus receptor (CAR) in inflammatory bowel disease (IBD). Background CAR, a type I transmembrane protein with functions in virus attachment, has been shown to be associated with epithelial tight junctions (TJs) and mediates cell adhesion, implying its potential roles in the pathogenesis of IBD. Methods and Materials To determine the effect of CAR in IBD using QPCR and Western blotting to determine the expression of CAD in TNF-α induced NCM460 and SW480 cells and IBD tissues compared to control groups. Furthermore, TJs dysregulation, FITC-Dextran permeability assay, qRT-PCR, Western blot, and IF assessed the permeability in CAR overexpressed cells treated with TNF-α. HE, qRT-PCR, Western blot, and IHC assay were used to assess the CAR overexpressed cells whether they have the effect to cure DSS induced ulcerative colitis rat model in vivo. Result We found CAR levels in human colon cell lines are significantly downregulated under the treatment of tumor necrosis factor-alpha (TNF-α). Furthermore, overexpression of CAR markedly prevented TNF-α induced inflammatory response, TJs dysregulation, and permeability disruption (FITC-Dextran permeability assay) in cells. Consistent with these findings in vitro, we found that CAR overexpression could suppress gut inflammation, attenuate the downregulation of TJ protein ZO-1 and Occludin, and limit the induction of barrier permeability in a DSS induced ulcerative colitis rat model in vivo. Together, our findings strongly suggest that CAR could protect tight junctions and has an anti-inflammatory effect during the pathogenesis of IBD. Thus CAR may serve as a therapeutic target for the diagnosis and treatment of IBD.
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