Varani et al., 2022

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

James Varani, Shannon D. McClintock and Muhammad N. Aslam*
The Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI, United States

Background:

The gastrointestinal tract barrier can be compromised in various inflammatory conditions like ulcerative colitis, crohn’s disease, irritable bowel syndrome, celiac disease and bacterial infections. These barrier defects can contribute to chronic inflammation. Certain structures in our cells, called tight junctions and desmosomes, help control the barrier’s permeability and strength. In previous studies, Aquamin improved the strength of these structures in human colon tissue (obtained from normal healthy subjects and UC patients). In this study, proteomic screening was used to examine how proteins involved in cell-matrix interactions behave in human colon organoid culture derived from either normal colon tissue or UC disease-affected tissue. Understanding these interactions can help us find ways to protect our digestive system.

Methods:

Human colon organoids were interrogated for transepithelial electrical resistance (TEER) under control conditions and in the presence of Aquamin. 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.

Results:

The findings in this study demonstrate that interfering with cell-basement membrane interactions reduces electrical resistance across the cell layer (a measure of permeability control) without a major effect on tissue cohesion in human colon organoid culture. The findings also demonstrate that treating colon organoids with Aquamin increased the expression of several proteins related to the basement membrane and cell-matrix attachments while partially mitigating the consequences of interfering with cell- basement membrane interactions. Increasing the elaboration of critical barrier proteins is an important mechanism by which Aquamin promotes barrier function.

Conclusions:

An intact barrier is required for healthy gastrointestinal function. While cell-cell adhesion structures are well-known participants in effective barrier function, the present study provides evidence that cell-matrix interactions are also important. These studies show, furthermore, that Aquamin has the capacity to stimulate the production of cell-matrix adhesion moieties and, concomitantly, to improve barrier control.

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