Closing the gap -- a two-tier mechanism for epithelial barrier

August 29, 2019

Okazaki, Japan - Epithelia are cell sheets that act as a barrier to protect our body from the external environment. Epithelial barrier is critical to maintain our body homeostasis, and its disruption has been linked to various diseases including atopic dermatitis and inflammatory bowel diseases. In order to maintain the epithelial barrier, it is important to completely seal the space between cells to restrict the movement of substances across the epithelial sheet - and that is the task that tight junctions fulfill.

Previous studies have identified claudins as a critical component of tight junctions. However, the roles of other molecules including JAM-A have been relatively unclear. In the study, the researchers utilized genome editing to systematically knockout claudins, and succeeded to generate epithelial cells lacking claudins for the first time.

In examining these cells, the researchers find that claudins form a barrier against small molecules including ions. To their surprise, loss of claudins did not lead to separation of the two neighboring cells; instead, the two membranes were closely attached to each other, and the barrier against larger molecules such as proteins was still maintained.

"We were puzzled with the results, as claudins were thought to be critical for the epithelial barrier", said the first author Tetsuhisa Otani. "However, when we noticed that JAM-A was more accumulated at cell junctions lacking claudins, we started to think that JAM-A may be maintaining the barrier against large molecules", he said.

To test the idea, the researchers further removed JAM-A from the claudin-deficient cells. Indeed, removal of JAM-A led to an expansion of the space between two neighboring cells, and to a disruption of the barrier against large molecules.

Mikio Furuse, the leading scientist of the study says "The study shows that epithelial barrier is made by a combination of two distinct systems: a tight barrier against small molecules made by claudins, and a crude barrier against large molecules made by JAM-A. This challenges the textbook view of tight junctions and epithelial barrier, and may impact our understanding of many diseases with problems in the epithelial barrier".
-end-


National Institutes of Natural Sciences

Related Diseases Articles from Brightsurf:

Understanding the spread of infectious diseases
Physicists at M√ľnster University (Germany) have shown in model simulations that the COVID-19 infection rates decrease significantly through social distancing.

Parkinson's disease is not one, but two diseases
Researchers around the world have been puzzled by the different symptoms and varied disease pathways of Parkinson's patients.

New gene implicated in neuron diseases
Healthy NEMF helps the cell recycle garbled protein fragments. But several mutant forms resulted in neuromuscular, neurodegenerative or other ALS-like disease, the scientists found.

Stretching your legs may help prevent diseases such as heart diseases and diabetes
New research published today in The Journal of Physiology shows that 12 weeks of easy-to-administer passive stretching helps improve blood flow by making it easier for your arteries to dilate and decreasing their stiffness.

Not all multiple sclerosis-like diseases are alike
Scientists say some myelin-damaging disorders have a distinctive pathology that groups them into a unique disease entity.

How many rare diseases are there?
Dr. Tudor Oprea says a better method for classifying rare diseases will lead to improved patient care.

A vaccine against chronic inflammatory diseases
In animals, a vaccine modifying the composition and function of the gut microbiota provides protection against the onset of chronic inflammatory bowel diseases and certain metabolic disorders, such as diabetes and obesity.

Ants fight plant diseases
New research from Aarhus University shows that ants inhibit at least 14 different plant diseases.

New, noninvasive test for bowel diseases
Gut diseases such as inflammatory bowel disease (IBD) are increasingly prevalent worldwide, especially in industrialized countries.

What is known -- and not known -- about heart muscle diseases in children
Cardiomyopathies (heart muscle diseases) in children are the focus of a new scientific statement from the American Heart Association that provides insight into the diagnosis and treatment of the diseases as well as identifying future research priorities.

Read More: Diseases News and Diseases Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.