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PLoS One. 2015 Jul 30;10(7):e0133926. doi: 10.1371/journal.pone.0133926. eCollection 2015.

Remodeling of Tight Junctions and Enhancement of Barrier Integrity of the CACO-2 Intestinal Epithelial Cell Layer by Micronutrients.

Author information

1
Lankenau Institute for Medical Research, Wynnewood, PA, 19096, United States of America.
2
Department of Biology, Drexel University, Philadelphia, PA, 19104, United States of America.
3
Janssen Research & Development, LLC, Spring House, PA, 19477, United States of America.
4
Lankenau Institute for Medical Research, Wynnewood, PA, 19096, United States of America; Division of Gastroenterology, Lankenau Medical Center, Wynnewood, PA, 19096, United States of America.

Abstract

The micronutrients zinc, quercetin, butyrate, indole and berberine were evaluated for their ability to induce remodeling of epithelial tight junctions (TJs) and enhance barrier integrity in the CACO-2 gastrointestinal epithelial cell culture model. All five of these chemically very diverse micronutrients increased transepithelial electrical resistance (Rt) significantly, but only berberine also improved barrier integrity to the non-electrolyte D-mannitol. Increases of Rt as much as 200% of untreated controls were observed. Each of the five micronutrients also induced unique, signature-like changes in TJ protein composition, suggesting multiple pathways (and TJ arrangements) by which TJ barrier function can be enhanced. Decreases in abundance by as much as 90% were observed for claudin-2, and increases of over 300% could be seen for claudins -5 and -7. The exact effects of the micronutrients on barrier integrity and TJ protein composition were found to be highly dependent on the degree of differentiation of the cell layer at the time it was exposed to the micronutrient. The substratum to which the epithelial layer adheres was also found to regulate the response of the cell layer to the micronutrient. The implications of these findings for therapeutically decreasing morbidity in Inflammatory Bowel Disease are discussed.

PMID:
26226276
PMCID:
PMC4520484
DOI:
10.1371/journal.pone.0133926
[Indexed for MEDLINE]
Free PMC Article

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