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Regulation of intestinal epithelial permeability by tight junctions

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Abstract

The gastrointestinal epithelium forms the boundary between the body and external environment. It effectively provides a selective permeable barrier that limits the permeation of luminal noxious molecules, such as pathogens, toxins, and antigens, while allowing the appropriate absorption of nutrients and water. This selective permeable barrier is achieved by intercellular tight junction (TJ) structures, which regulate paracellular permeability. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, and can act as a trigger for the development of intestinal and systemic diseases. In this context, much effort has been taken to understand the roles of extracellular factors, including cytokines, pathogens, and food factors, for the regulation of the intestinal TJ barrier. Here, I discuss the regulation of the intestinal TJ barrier together with its implications for the pathogenesis of diseases.

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Abbreviations

AJ:

Adherens junction

ALD:

Alcoholic liver disease

AMPK:

AMP activated protein kinase

BBDP:

Biobreeding diabetes-prone

BiCM:

Conditioned medium of Bifidobacterium infantis

BT-IgSF:

Brain- and testis-specific immunoglobulin superfamily

C10:

Capric acid

C12:

Lauric acid

CAR:

Coxsacki and adenovirus receptor

CD:

Crohn’s disease

CHO:

Chinese hamster ovary

CPE:

Clostridium perfringen enterotoxin

DHA:

Docosahexaenoic acid

DSS:

Dextran sodium sulfate

ECN:

Escherichia coli Nissle1917

EGF:

Epidermal growth factor

EHEC:

Enterohemorrhagic Escherichia coli

EPA:

Eicosapentaenoic acid

EPEC:

Enteropathogenic Escherichia coli

ERK:

Extracellular signal-regulated kinase

ESAM:

Endothelial selective adhesion molecule

EspF:

Escherichia coli secreted protein F

GPCR:

G-protein-coupled receptor

HA/P:

Hemagglutinin/protease

HS/R:

Hemorrhagic shock and resuscitation

IBD:

Inflammatory bowel disease

IBS:

Irritative bowel syndrome

IFN:

Interferon

Ig:

Immunoglobulin

IL:

Interleukin

JAM:

Junctional adhesion molecule

LA:

Linolec acid

LCFA:

Long chain fatty acid

LIGHT:

Lymphotoxin-like inducible protein

L. plantarum :

Lactobacillus plantarum

L. rhamnosus :

Lactobacillus rhamnosus

MAGUK:

Membrane-associated guanylate kinase homolog

MAP:

Mitochondrial-associated protein

MCFA:

Medium chain fatty acid

MEK:

Mitogen-activated protein kinase

MLC:

Myosin light chain

MLCK:

Myosin light chain kinase

NFκB:

Nuclear factor-κB

PAR:

Proteinase activated receptor

PDZ:

Post-synaptic density 95/Drosophila discs large/zona-occludens 1

PI3K:

Phosphatidyl inositol-3 kinase

PK:

Protein kinase

PKA:

cAMP-dependent kinase

PP:

Protein phosphatase

PPAR:

Peroxisome proliferator-activated receptor

PTP:

Protein tyrosine phosphatase

ROCK:

Rho-associated kinase

SCFA:

Short chain fatty acid

SH:

Src homology

T1D:

Type I diabetes

TER:

Transepithelial electrical resistance

TGF:

Transforming growth factor

TJ:

Tight junction

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TNFR:

TNF-α receptor

TPN:

Total parenteral nutrition

VDR:

Vitamin D receptor

ZO:

Zonula occludens

ZOT:

Zonula occludens toxin

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Acknowledgments

This work was supported by Japan Society for the Promotion of Science, a Grant-in-Aid for Young Scientists (B) 23780135 to T. Suzuki.

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  1. Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, 1-4-4, Kagamiyama, Higashi-Hiroshima, 739-8528, Japan

    Takuya Suzuki

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Suzuki, T. Regulation of intestinal epithelial permeability by tight junctions. Cell. Mol. Life Sci. 70, 631–659 (2013). https://doi.org/10.1007/s00018-012-1070-x

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