Cell-Matrix Interactions Contribute to Barrier Function in Human Colon Organoids.

Cell-Matrix Interactions Contribute to Barrier Function in Human Colon Organoids.
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细胞-基质相互作用对人结肠类器官的屏障功能起作用。

DOI:
10.3389/fmed.2022.838975
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发表时间:
2022
影响因子:
3.9
通讯作者:
Aslam MN
Aslam MN
中科院分区:
医学3区
文献类型:
--
作者:
Varani J;McClintock SD;Aslam MN

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细胞-基质粘附对结肠屏障控制的重要性尚不清楚。本研究的目的是:(i)确定结肠上皮细胞与细胞外基质相互作用的破坏是否会改变渗透性控制测量,以及(ii)确定增加细胞-基质粘附复合物蛋白组分的加工是否可以减轻细胞-基质破坏的影响。在对照条件下和在Aquamin®(一种多矿物质产品)存在下询问人结肠类器官的跨上皮电阻(TEER)。平行使用针对层粘连蛋白α链C-末端区域的功能阻断抗体。在蛋白质组筛选中并通过蛋白质印迹法测定Aquamin®对细胞-基质粘附蛋白表达的影响。Aquamin®增加了多种基底膜、半桥粒和粘着斑蛋白以及角蛋白8和18的表达。在Aquamin®存在下的TEER值高于在对照条件下的TEER值。封闭抗体在两种条件下都降低了TEER值,但在不存在Aquamin®的情况下最有效,其中细胞基质粘附蛋白的表达在开始时较低。这些发现提供了细胞-基质相互作用有助于结肠屏障控制的证据。
The importance of cell-matrix adhesion to barrier control in the colon is unclear. The goals of the present study were to: (i) determine if disruption of colon epithelial cell interactions with the extracellular matrix alters permeability control measurement and (ii) determine if increasing the elaboration of protein components of cell-matrix adhesion complexes can mitigate the effects of cell-matrix disruption. Human colon organoids were interrogated for transepithelial electrical resistance (TEER) under control conditions and in the presence of Aquamin®, a multi-mineral product. A function-blocking antibody directed at the C-terminal region of the laminin α chain was used in parallel. The effects of Aquamin® on cell-matrix adhesion protein expression were determined in a proteomic screen and by Western blotting. Aquamin® increased the expression of multiple basement membrane, hemidesmosomal and focal adhesion proteins as well as keratin 8 and 18. TEER values were higher in the presence of Aquamin® than they were under control conditions. The blocking antibody reduced TEER values under both conditions but was most effective in the absence of Aquamin®, where expression of cell-matrix adhesion proteins was lower to begin with. These findings provide evidence that cell-matrix interactions contribute to barrier control in the colon.
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发表时间: 2017-12
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