Intestinal Permeability Regulation by Tight Junction: Implication on Inflammatory Bowel Diseases

Overview

Journal Intest Res

Date 2015 Feb 19

PMID 25691839

Citations 315

Authors

Sung Hee Lee

Affiliations

Soon will be listed here.

Abstract

Epithelial tight junctions (TJs) are the key structures regulating paracellular trafficking of macromolecules. The TJ is multi-protein complex that forms a selective permeable seal between adjacent epithelial cells and demarcates the boundary between apical and basolateral membrane domains. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, which can act as a trigger for the development of intestinal and systemic diseases. Inflammatory bowel disease (IBD) patients demonstrate increased intestinal paracellular permeability. Although it remains unclear whether barrier dysfunction precedes disease or results from active inflammation, increased intestinal TJ disruption is observed in IBD patients suggest that dysregulation of TJ barrier integrity may predispose or enhance IBD progression. Therefore, therapeutic target to restore the TJ barrier integrity may provide effective therapeutic and preventive approaches against IBD. This review discusses the molecular structure and regulation of intestinal TJs and the involvement of intestinal TJs in IBD pathogenesis.

Citing Articles

ARNT-dependent HIF-2α signaling protects cardiac microvascular barrier integrity and heart function post-myocardial infarction.

Ullah K, Ai L, Li Y, Liu L, Zhang Q, Pan K Commun Biol. 2025; 8(1):440.

PMID: 40089572 DOI: 10.1038/s42003-025-07753-1.

The Neonatal Microbiome: Implications for Amyotrophic Lateral Sclerosis and Other Neurodegenerations.

Eisen A, Kiernan M Brain Sci. 2025; 15(2).

PMID: 40002527 PMC: 11852589. DOI: 10.3390/brainsci15020195.

Exacerbation of polyethylene microplastics in animal models of DSS-induced colitis through damage to intestinal epithelial cell conjunctions.

Sung M, Lee Y, Sung S, Kang K, Park J, Lee Y Curr Res Toxicol. 2025; 8:100217.

PMID: 39944107 PMC: 11815690. DOI: 10.1016/j.crtox.2025.100217.

Alterations in mucosa branched -glycans lead to dysbiosis and downregulation of ILC3: a key driver of intestinal inflammation.

Rodrigues C, Gaifem J, Pereira M, Alves M, Silva M, Padrao N Gut Microbes. 2025; 17(1):2461210.

PMID: 39918275 PMC: 11810091. DOI: 10.1080/19490976.2025.2461210.

Role of polyamines in intestinal mucosal barrier function.

Nakamura A, Matsumoto M Semin Immunopathol. 2025; 47(1):9.

PMID: 39836273 PMC: 11750915. DOI: 10.1007/s00281-024-01035-4.

References

Sakakibara A, Furuse M, Saitou M, Ando-Akatsuka Y, Tsukita S . Possible involvement of phosphorylation of occludin in tight junction formation. J Cell Biol. 1997; 137(6):1393-401. PMC: 2132539. DOI: 10.1083/jcb.137.6.1393. View

Walsh S, Hopkins A, Chen J, Narumiya S, Parkos C, Nusrat A . Rho kinase regulates tight junction function and is necessary for tight junction assembly in polarized intestinal epithelia. Gastroenterology. 2001; 121(3):566-79. DOI: 10.1053/gast.2001.27060. View

Suenaert P, Bulteel V, Lemmens L, Noman M, Geypens B, Van Assche G . Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease. Am J Gastroenterol. 2002; 97(8):2000-4. DOI: 10.1111/j.1572-0241.2002.05914.x. View

Blair S, Kane S, Clayburgh D, Turner J . Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Lab Invest. 2006; 86(2):191-201. DOI: 10.1038/labinvest.3700373. View

Al-Sadi R, Ye D, Dokladny K, Ma T . Mechanism of IL-1beta-induced increase in intestinal epithelial tight junction permeability. J Immunol. 2008; 180(8):5653-61. PMC: 3035485. DOI: 10.4049/jimmunol.180.8.5653. View

Gonzalez-Mariscal L, Betanzos A, Nava P, Jaramillo B . Tight junction proteins. Prog Biophys Mol Biol. 2002; 81(1):1-44. DOI: 10.1016/s0079-6107(02)00037-8. View

Willott E, Balda M, Fanning A, Jameson B, Van Itallie C, Anderson J . The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc Natl Acad Sci U S A. 1993; 90(16):7834-8. PMC: 47237. DOI: 10.1073/pnas.90.16.7834. View

Laukoetter M, Nava P, Lee W, Severson E, Capaldo C, Babbin B . JAM-A regulates permeability and inflammation in the intestine in vivo. J Exp Med. 2007; 204(13):3067-76. PMC: 2150975. DOI: 10.1084/jem.20071416. View

Kansagra K, Stoll B, Rognerud C, Niinikoski H, Ou C, Harvey R . Total parenteral nutrition adversely affects gut barrier function in neonatal piglets. Am J Physiol Gastrointest Liver Physiol. 2003; 285(6):G1162-70. DOI: 10.1152/ajpgi.00243.2003. View

10.

Schulzke J, Bojarski C, Zeissig S, Heller F, Gitter A, Fromm M . Disrupted barrier function through epithelial cell apoptosis. Ann N Y Acad Sci. 2006; 1072:288-99. DOI: 10.1196/annals.1326.027. View

11.

Farhadi A, Banan A, Fields J, Keshavarzian A . Intestinal barrier: an interface between health and disease. J Gastroenterol Hepatol. 2003; 18(5):479-97. DOI: 10.1046/j.1440-1746.2003.03032.x. View

12.

Furuse M, Itoh M, Hirase T, Nagafuchi A, Yonemura S, Tsukita S . Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J Cell Biol. 1994; 127(6 Pt 1):1617-26. PMC: 2120300. DOI: 10.1083/jcb.127.6.1617. View

13.

Umeda K, Matsui T, Nakayama M, Furuse K, Sasaki H, Furuse M . Establishment and characterization of cultured epithelial cells lacking expression of ZO-1. J Biol Chem. 2004; 279(43):44785-94. DOI: 10.1074/jbc.M406563200. View

14.

Martinez-Gonzalez O, Cantero-Hinojosa J . Intestinal permeability in patients with ankylosing spondylitis and their healthy relatives. Br J Rheumatol. 1994; 33(7):644-7. DOI: 10.1093/rheumatology/33.7.644. View

15.

Cunningham S, Arrate M, Rodriguez J, Bjercke R, Vanderslice P, Morris A . A novel protein with homology to the junctional adhesion molecule. Characterization of leukocyte interactions. J Biol Chem. 2000; 275(44):34750-6. DOI: 10.1074/jbc.M002718200. View

16.

Zeissig S, Burgel N, Gunzel D, Richter J, Mankertz J, Wahnschaffe U . Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut. 2006; 56(1):61-72. PMC: 1856677. DOI: 10.1136/gut.2006.094375. View

17.

Pappu R, Ramirez-Carrozzi V, Sambandam A . The interleukin-17 cytokine family: critical players in host defence and inflammatory diseases. Immunology. 2011; 134(1):8-16. PMC: 3173690. DOI: 10.1111/j.1365-2567.2011.03465.x. View

18.

Tsukita S, Furuse M . Pores in the wall: claudins constitute tight junction strands containing aqueous pores. J Cell Biol. 2000; 149(1):13-6. PMC: 2175101. DOI: 10.1083/jcb.149.1.13. View

19.

Bruewer M, Utech M, Ivanov A, Hopkins A, Parkos C, Nusrat A . Interferon-gamma induces internalization of epithelial tight junction proteins via a macropinocytosis-like process. FASEB J. 2005; 19(8):923-33. DOI: 10.1096/fj.04-3260com. View

20.

Jain S, Suzuki T, Seth A, Samak G, Rao R . Protein kinase Cζ phosphorylates occludin and promotes assembly of epithelial tight junctions. Biochem J. 2011; 437(2):289-99. PMC: 3408004. DOI: 10.1042/BJ20110587. View