Varani James, McClintock Shannon D, Aslam Muhammad N
The Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI, United States.
Front Med (Lausanne). 2022 Mar 10;9:838975. doi: 10.3389/fmed.2022.838975. eCollection 2022.
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.
细胞与基质的黏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的相互作用破坏是否会改变通透性控制测量结果，以及（ii）确定增加细胞-基质黏附复合物蛋白质成分的生成是否可以减轻细胞-基质破坏的影响。在对照条件下以及在存在多矿物质产品Aquamin®的情况下，检测人结肠类器官的跨上皮电阻（TEER）。同时使用针对层粘连蛋白α链C末端区域的功能阻断抗体。通过蛋白质组学筛选和蛋白质印迹法确定Aquamin®对细胞-基质黏附蛋白表达的影响。Aquamin®增加了多种基底膜、半桥粒和黏着斑蛋白以及角蛋白8和18的表达。在存在Aquamin®的情况下，TEER值高于对照条件下的值。阻断抗体在两种条件下均降低了TEER值，但在没有Aquamin®的情况下最有效，因为在这种情况下细胞-基质黏附蛋白的表达一开始就较低。这些发现提供了证据，表明细胞-基质相互作用有助于结肠的屏障控制。
