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Home»News»Understanding the mechanisms behind cystic fibrosis infections
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Understanding the mechanisms behind cystic fibrosis infections

healthtostBy healthtostApril 5, 2024No Comments3 Mins Read
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Understanding The Mechanisms Behind Cystic Fibrosis Infections
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Cystic fibrosis is a genetic disease that causes severe and sometimes fatal respiratory and digestive disorders. A new treatment, available from 2020, improves lung function and quality of life. However, it does not always eliminate the bacteria responsible for respiratory infections. By studying 3D models of human lung cells, scientists at the University of Geneva (UNIGE) discovered that this drug does not prevent the development on the surface of the respiratory tract of “docking stations” to which bacteria attach to infect the body. . These junctions result from disruption of signals involved in cell growth in the respiratory system. By combining the current treatment with other molecules, it may be possible to restore cellular balance and thus better prevent bacterial infections. These results are published on American Journal of Respiratory Cell and Molecular Biology.

Cystic fibrosis is the most common genetic disease. Each year, it affects one in 3,300 newborns in Switzerland. Mutations in the gene responsible for the CFTR protein cause the secretion of excessively thick mucus, which blocks the airways. Although a triple therapy, available in Switzerland since 2020, has improved the quality of life of people with cystic fibrosis, it is not suitable for all sufferers and does not always prove effective.

“A significant proportion of people receiving this treatment still suffer from residual inflammation and persistent respiratory infections. Understanding the reasons for this is essential if we want to improve patient care,” explains Marc Chanson, full professor in the Department of Cellular Physiology and Metabolism at UNIGE Medical School and member of the Geneva Inflammation Research Center, who led this research . .

Imbalance in cellular signals

In previous studies, Marc Chanson’s team had discovered that respiratory cells affected by cystic fibrosis build up docking stations on their surface that allow the bacteria to anchor firmly in the lungs. “So we wanted to know if the triple therapy had an effect on this mechanism, which is so predisposing to bacterial infection,” explains Mehdi Badaoui, researcher and professor in the Department of Cellular Physiology and Metabolism at the UNIGE School of Medicine. and last author of the study.

By comparing 3D models of human lung cells—healthy cells as well as cells with cystic fibrosis—the scientists demonstrated that the triple therapy currently used does not prevent the formation of these junctions. Indeed, gene expression in healthy cells, compared to cystic fibrosis cells, shows an imbalance between two cell signaling pathways: the TGF-β pathway is overactivated, while the Wnt pathway is inhibited. Cell signaling pathways support the development of all multicellular organisms, including humans. Without them, cells cannot grow and function properly.

By uncovering a disruption in these signaling pathways, the research team shed light on a key mechanism: diseased cells do not receive the proper signals and react by creating junctions that are harmful to them. By restoring the balance between these two cell signaling pathways, the scientists were able to significantly reduce the growth of these structures.

If we can identify a drug compound able to restore this balance in patients, we could combine it with the current triple therapy to increase its effectiveness and limit bacterial infections while reducing its side effects.”

Marc Chanson, Full Professor in the Department of Cell Physiology and Metabolism at UNIGE School of Medicine

Source:

Journal Reference:

Idris, T., et al. (2024). Akt-driven secretion of TGF-β and DKK1 affects polarity of F508del CF airway epithelium. American Journal of Respiratory Cell and Molecular Biology. doi.org/10.1165/rcmb.2023-0408oc.

cystic fibrosis infections mechanisms Understanding
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