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

Research output: Contribution to journalArticle

43 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

Fingerprint

Tight Junctions
Chitosan
Caco-2 Cells
Cell membranes
Permeation
Integrins
Monolayers
Permeability
Cell Membrane
Derivatives
Tight Junction Proteins
Phosphorylation
src-Family Kinases
Macromolecules
Cytosol
Biological Availability
Cluster Analysis
Epithelial Cells
Chemical activation
Proteins

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., ... 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

Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan. / Hsu, Li Wen; Lee, Pei Ling; Chen, Chiung Tong; Mi, Fwu Long; Juang, Jyuhn Huarng; Hwang, Shiaw Min; Ho, Yi Cheng; Sung, Hsing Wen.

In: Biomaterials, Vol. 33, No. 26, 09.2012, p. 6254-6263.

Research output: Contribution to journalArticle

Hsu, LW, Lee, PL, Chen, CT, Mi, FL, Juang, JH, Hwang, SM, Ho, YC & Sung, HW 2012, 'Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan', Biomaterials, vol. 33, no. 26, pp. 6254-6263. https://doi.org/10.1016/j.biomaterials.2012.05.013
Hsu, Li Wen ; Lee, Pei Ling ; Chen, Chiung Tong ; Mi, Fwu Long ; Juang, Jyuhn Huarng ; Hwang, Shiaw Min ; Ho, Yi Cheng ; Sung, Hsing Wen. / Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan. In: Biomaterials. 2012 ; Vol. 33, No. 26. pp. 6254-6263.
@article{2ca412336b8441b6ae3c2985b8c5801e,
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 = "Chitosan, Integrin receptor, Oral drug delivery, Paracellular permeability, Tyrosine kinase",
author = "Hsu, {Li Wen} and Lee, {Pei Ling} and Chen, {Chiung Tong} and Mi, {Fwu Long} and Juang, {Jyuhn Huarng} and Hwang, {Shiaw Min} and Ho, {Yi Cheng} and Sung, {Hsing Wen}",
year = "2012",
month = "9",
doi = "10.1016/j.biomaterials.2012.05.013",
language = "English",
volume = "33",
pages = "6254--6263",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier Science Ltd",
number = "26",

}

TY - JOUR

T1 - Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan

AU - Hsu, Li Wen

AU - Lee, Pei Ling

AU - Chen, Chiung Tong

AU - Mi, Fwu Long

AU - Juang, Jyuhn Huarng

AU - Hwang, Shiaw Min

AU - Ho, Yi Cheng

AU - Sung, Hsing Wen

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

KW - Chitosan

KW - Integrin receptor

KW - Oral drug delivery

KW - Paracellular permeability

KW - Tyrosine kinase

UR - http://www.scopus.com/inward/record.url?scp=84862842747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862842747&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2012.05.013

DO - 10.1016/j.biomaterials.2012.05.013

M3 - Article

C2 - 22681978

AN - SCOPUS:84862842747

VL - 33

SP - 6254

EP - 6263

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 26

ER -