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

Li Wen Hsu, Pei Ling Lee, Chiung Tong Chen, Fwu Long Mi, Jyuhn Huarng Juang, Shiaw Min Hwang, Yi Cheng Ho, Hsing Wen Sung

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46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6254-6263
Number of pages10
JournalBiomaterials
Volume33
Issue number26
DOIs
Publication statusPublished - Sep 2012
Externally publishedYes

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Keywords

  • Chitosan
  • Integrin receptor
  • Oral drug delivery
  • Paracellular permeability
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Hsu, L. W., Lee, P. L., Chen, C. T., Mi, F. L., Juang, J. H., Hwang, S. M., Ho, Y. C., & Sung, H. W. (2012). Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan. Biomaterials, 33(26), 6254-6263. https://doi.org/10.1016/j.biomaterials.2012.05.013