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Cell-matrix adhesion contributes to permeability control in human colon organoids

James Varani, Shannon D. McClintock, View ORCID ProfileMuhammad N. Aslam
doi: https://doi.org/10.1101/2021.06.11.448147
James Varani
The Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109
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Shannon D. McClintock
The Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109
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Muhammad N. Aslam
The Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109
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  • ORCID record for Muhammad N. Aslam
  • For correspondence: mnaslam@med.umich.edu
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ABSTRACT

Background and aims Cell-cell adhesion structures (desmosomes and, especially, tight junctions) are known to play important roles in control of transepithelial permeability in the colon. The involvement of cell-matrix interactions in permeability control is less clear. The goals of the present study were to: i) determine if disruption of colon epithelial cell interactions with the extracellular matrix alters permeability control and ii) determine if increasing the elaboration of protein components of cell-matrix adhesion complexes improves permeability control and mitigates the effects of cell-matrix disruption.

Methods Human colon organoids were interrogated for transepithelial electrical resistance (TEER) under control conditions (0.25 mM calcium) and in the presence of Aquamin®, a multi-mineral product, at a level providing 1.5 mM calcium. The effects of Aquamin® on cell-matrix adhesion protein expression were determined in a proteomic screen and by Western blotting. In parallel, TEER was assessed in the presence of a function-blocking antibody directed at an epitope in the C-terminal region of laminin α3 chain.

Results Treatment of colon organoids with Aquamin® increased the expression of multiple basement membrane and hemidesmosomal proteins as well as keratin 8 and 18. TEER values were higher in the presence of Aquamin® than they were under control conditions. Anti-laminin antibody reduced TEER values under all conditions but was most effective in the absence of Aquamin®, where laminin expression was low and TEER values were lower to begin with.

Conclusions These findings provide evidence that cell-matrix interactions contribute to permeability control in the colon. They suggest that the elaboration of proteins important to cell-matrix interactions can be increased in human colon organoids by exposure to a multi-mineral natural product. Increasing the elaboration of such proteins may help to mitigate the consequences of disrupting cell-matrix interactions on permeability control.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 11, 2021.
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Cell-matrix adhesion contributes to permeability control in human colon organoids
James Varani, Shannon D. McClintock, Muhammad N. Aslam
bioRxiv 2021.06.11.448147; doi: https://doi.org/10.1101/2021.06.11.448147
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Cell-matrix adhesion contributes to permeability control in human colon organoids
James Varani, Shannon D. McClintock, Muhammad N. Aslam
bioRxiv 2021.06.11.448147; doi: https://doi.org/10.1101/2021.06.11.448147

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