Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 489951
Title Activation of the Epithelial-to-Mesenchymal Transition Factor Snail Mediated Acetaldehyde-Induced Intestinal Epithelial Barrier Disruption
Author(s) Elamin, E.; Masclee, A.; Troost, F.; Dekker, J.; Jonkers, D.
Source Alcoholism : Clinical and Experimental Research 38 (2014)2. - ISSN 0145-6008 - p. 344 - 353.
DOI https://doi.org/10.1111/acer.12234
Department(s) Department of Animal Sciences
Publication type Refereed Article in a scientific journal
Publication year 2014
Keyword(s) transcription factor snail - caco-2 cell monolayers - tight junctions - paracellular permeability - in-vitro - adherens junctions - ethanol oxidation - colonic flora - expression - cirrhosis
Abstract Background : Acetaldehyde (AcH) is mutagenic and can reach high concentrations in colonic lumen after ethanol consumption and is associated with intestinal barrier dysfunction and an increased risk of progressive cancers, including colorectal carcinoma. Snail, the transcription factor of epithelial-mesenchymal transition, is known to down-regulate expression of tight junction (TJ) and adherens junction (AJ) proteins, resulting in loss of epithelial integrity, cancer progression, and metastases. As AcH is mutagenic, the role of Snail in the AcH-induced disruption of intestinal epithelial TJs deserves further investigation. Our aim was to investigate the role of oxidative stress and Snail activation in AcH-induced barrier disruption in Caco-2 monolayers. Methods : The monolayers were exposed from the apical side to AcHL-cysteine. Reactive oxygen species (ROS) generation and Snail activation were assessed by ELISA and immunofluorescence. Paracellular permeability, localization, and expression of ZO-1, occludin, E-cadherin, and -catenin were examined using transepithelial electrical resistance (TEER), fluorescein isothiocyanate-labeled dextran 4 kDa (FITC-D4), immunofluorescence, and ELISA, respectively. Involvement of Snail was further addressed by inhibiting Snail using small interfering RNA (siRNA). Results : Exposure to 25M AcH increased ROS generation and ROS-dependently induced Snail phosphorylation. In addition, AcH increased paracellular permeability (decrease in TEER and increase in FITC-D4 permeation) in association with redistribution and decrease of TJ and AJ protein levels, which could be attenuated by L-cysteine. Knockdown of Snail by siRNA attenuated the AcH-induced redistribution and decrease in the TJ and AJ proteins, in association with improvement of the barrier function. Conclusions : Our data demonstrate that oxidative stress-mediated Snail phosphorylation is likely a novel mechanism contributing to the deleterious effects of AcH on the TJ and AJ, and intestinal barrier function.
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