Saturday, October 1, 2022

Cystic fibrosis: restoring the integrity of the airway

Cystic fibrosis is a rare genetic disease that can cause very severe symptoms. In particular, patients suffer from chronic bacterial infections that can lead to respiratory failure. It is caused by a mutation in the CFTR gene, which controls the movement of water across the cell membrane. As a result, the quality of the mucus changes, it is no longer able to capture unwanted bacteria and flush them out. Using a model reproducing a respiratory epithelium – a protective tissue composed of a monolayer of cells – teams from the University of Geneva (UNIGE) have found that a simple film of liquid can help restore airway seal and protect against risk. enough to reduce it. bacterial infection.

These results to be read in the special issue of the magazine Cells, open the way for new treatments based on mucus hydration. A promising alternative to current treatments that are often not effective enough widely.

Despite recent medical advances, people with cystic fibrosis – one in every 2,500 births in Europe – have a life expectancy of no more than 46 years and a change in quality of life. The disease is caused by one or more mutations in the CFTR gene, which affect the proper functioning of an essential protective barrier. Epithelial cells that line the airway are usually sealed together and thus protect the airway from bacterial colonization. They are also lined with a fluid, a slippery mucus that traps unwanted germs and carries them away. When the CFTR protein is altered, the junctions between cells loosen and dehydrated mucus stagnates, both of which promote the development of respiratory infections.

“While it was already known that mucus hydration and the presence of sufficiently tight junctions preserved airway integrity, the mechanisms involved and the relationship between these two mechanisms remained mysterious, hindering the development of new therapies.” ,” explains Mark Chanson, a professor in the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine and the Geneva Center for Inflammation Research, who led this research.

Hydrating to restore tightness

The scientists first developed an in vitro model using human lung cells. This model, which was awarded the UNIGE 3R Prize in 2021 for reducing animal experimentation, reproduces the airway epithelium of healthy and cystic fibrosis patients in a way that is accurate and close to clinical reality. is close. In collaboration with the team of Christian van Delden and Thilo Köhler of the Department of Medicine and Microbiology and Molecular Medicine at the UNIGE Faculty of Medicine, Mark Chanson and his team compared the response of invalidated epithelial cells to CFTR with bacterial infection, causing either hydrated , healthy mucus or physiological saline solution was added.

Juliet Simonin, a post-doctoral fellow in Mark Chanson’s lab and first author of the study, explains, “We observed a similar response in both cases: the presence of the liquid, whatever its composition, restores the airways and protects them from infection. is.” “Surface hydration is sufficient to tighten the junctions between cells and protect epithelial integrity from bacterial colonization even when CFTR is not functioning.”

One treatment for all mutations?

A triple therapy pharmacologically targeting the CFTR protein has recently become available on the market. However, it only targets certain mutations of the CFTR gene and is only prescribed for a specific population of people with cystic fibrosis. More widely effective and safe treatments are still sorely lacking.

“Our results provide evidence that airway surface rehydration is beneficial. The challenge now is to find a simple way to do this in all people with the disease, regardless of the mutation involved,” concluded Mark Chanson. .

Story Source:

material provided by university de geneve, Note: Content can be edited for style and length.

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