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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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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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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DOI: https://doi.org/10.1007/s00018-012-1070-x