DDS: IL-17A可以通过上皮-间质转化促进肠纤维化的发生和发展

2018-11-19 MedSci MedSci原创

肠纤维化是克罗恩病(CD)的常见并发症。其确切机制尚不清楚,目前还没有有效的控制或逆转纤维化过程的治疗方法。上皮 - 间质转化(EMT)可通过增加细胞外基质蛋白的沉积来促进肠纤维化。IL-17A是促炎性细胞因子,并且已经显示其作为促纤维化因子,因此本项研究旨在探索IL-17A与肠纤维化之间的联系。

背景
肠纤维化是克罗恩病(CD)的常见并发症。其确切机制尚不清楚,目前还没有有效的控制或逆转纤维化过程的治疗方法。上皮 - 间质转化(EMT)可通过增加细胞外基质蛋白的沉积来促进肠纤维化。IL-17A是促炎性细胞因子,并且已经显示其作为促纤维化因子,因此本项研究旨在探索IL-17A与肠纤维化之间的联系。

方法
在本研究中,研究人员评估了CD患者和对照个体的结肠粘膜活检组织中IL-17A和EMT相关基因的表达水平。然后,检测了在增加浓度的IL-17A或TGF-β1培养72小时后,IEC-6细胞的EMT相关基因和纤维化相关基因的变化,以验证IL-17A的潜在诱导作用。 EMT的体外实验中,研究人员阻断了TNBS诱导的实验性肠结肠炎和纤维化小鼠模型的IL-17A,以进一步验证IL-17A对体内EMT的潜在诱导作用。

结果
研究人员在CD患者的肠粘膜中发现了EMT和IL-17A的高水平表达。使用IEC-6细胞,我们发现IL-17A可以诱导肠上皮细胞中的EMT,其具有降低的E-钙粘蛋白表达和增加的波形蛋白,α-SMA的表达。我们进一步发现可以通过抗IL-17A治疗来减少小鼠肠中的EMT来减轻肠纤维化。

结论
本项研究证实了IL-17A通过诱导EMT参与肠纤维化的发展。

原始出处:
Hui-Jing Zhang. Et al. IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT. Digestive Diseases and Sciences.2018.

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    2018-11-20 fzwish20000
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    2018-11-20 jjjiang0202
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    2018-11-19 lovetcm

    炎症是因,纤维化是果

    0

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