Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan.
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.
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan 30013, ROC.
Li-Wen
LW
Hsu
Pei-Ling
PL
Lee
Chiung-Tong
CT
Chen
Fwu-Long
FL
Mi
Jyuhn-Huarng
JH
Juang
Shiaw-Min
SM
Hwang
Yi-Cheng
YC
Ho
Hsing-Wen
HW
Sung
D015153:Blotting, Western; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D048271:Chitosan / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*
D048271:Chitosan; D011505:Protein-Tyrosine Kinases