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Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan

Paper ID Volume ID Publish Year Pages File Format Full-Text
6725 513 2012 10 PDF Available
Title
Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan
Abstract

Chitosan (CS) and its derivatives have been investigated as paracellular permeation enhancers for facilitating the oral bioavailability of hydrophilic macromolecules. As is well known, CS can transiently open the tight junctions (TJs) between epithelial cells, thus enhancing the paracellular permeability. However, the signaling mechanism that is related to the effect of CS on TJs remains unclear. Therefore, this study elucidates the potential transduction cascade of TJ opening in Caco-2 cell monolayers subsequent to CS exposure. Experimental results indicate that activation of integrin receptors on cell membranes significantly contributes to CS-mediated TJ disruption, initiating the cascade of TJ opening. Additionally, treatment of Caco-2 cell monolayers with CS leads to the clustering of integrins along the cell border, phosphorylation of FAK and Src tyrosine kinases, and results in the regulation of TJ permeability via the redistribution of TJ protein CLDN4 from the cell membrane to the cytosol. Elucidating the signaling mechanism of CS-induced TJ opening in intestinal cells significantly contributes to efforts to use CS and its derivatives as paracellular permeation enhancers.

Keywords
Integrin receptor; Tyrosine kinase; Oral drug delivery; Paracellular permeability; Chitosan
First Page Preview
Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 26, September 2012, Pages 6254–6263
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering