Tight junctions and human diseases (original) (raw)

Abstract

Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

Access this article

Log in via an institution

Subscribe and save

• Get 10 units per month
• Download Article/Chapter or eBook
• 1 Unit = 1 Article or 1 Chapter
• Cancel anytime Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

1. Department of Pathology, Sapporo Medical University School of Medicine, S1, W17, Sapporo, 060-8556, Japan
   Norimasa Sawada, Masaki Murata, Keisuke Kikuchi, Makoto Osanai, Hirotoshi Tobioka, Takashi Kojima & Hideki Chiba

Authors

1. Norimasa Sawada
   You can also search for this author inPubMed Google Scholar
2. Masaki Murata
   You can also search for this author inPubMed Google Scholar
3. Keisuke Kikuchi
   You can also search for this author inPubMed Google Scholar
4. Makoto Osanai
   You can also search for this author inPubMed Google Scholar
5. Hirotoshi Tobioka
   You can also search for this author inPubMed Google Scholar
6. Takashi Kojima
   You can also search for this author inPubMed Google Scholar
7. Hideki Chiba
   You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toNorimasa Sawada.

Rights and permissions

About this article

Cite this article

Sawada, N., Murata, M., Kikuchi, K. et al. Tight junctions and human diseases.Med Electron Microsc 36, 147–156 (2003). https://doi.org/10.1007/s00795-003-0219-y

Download citation

• Received: 11 March 2003
• Accepted: 18 March 2003
• Issue Date: September 2003
• DOI: https://doi.org/10.1007/s00795-003-0219-y

Key words