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Keeping the intestine alive: FAU researchers decode self-destruct programme in intestinal mucosa

Microscopic image of intestinal epithelial cells in a petri dish. Without the molecule cFlip, the cells die en masse. Nuclei are shown in blue. (Image: Dr. Nadine Wittkopf, Department of Medicine 1)

Microscopic image of intestinal epithelial cells in a petri dish. Without the molecule cFlip, the cells die en masse. Nuclei are shown in blue. (Image: Dr. Nadine Wittkopf, Department of Medicine 1)

A healthy cell in the mucosa of the human intestine only lives for about three to five days. Then it dies and a new cell grows in its place. This sensitive balance between cellular death and renewal is extremely important for protecting the organism against severe disease. This is why the body has developed mechanisms that monitor the process of death and growth closely. FAU scientists have now been able to prove this and have thus discovered a new starting point for the treatment of diseases such as Crohn’s disease, ulcerative colitis and cancer.

Up to one hundred trillion bacteria – useful as well as harmful kinds – populate the human intestine. That is ten times more than the number of cells in the human body. The only barrier between the intestinal flora and the organism is formed by the cells of the intestinal mucosa, also known as epithelial cells, which die and are regenerated every three to five days. An imbalance between death and regrowth of the intestinal epithelial cells poses significant risks. If more cells die than are grown, bacteria penetrate into the body, possibly causing severe infection and tissue damage. Diseases such as Crohn’s, ulcerative colitis or cancer are possible results.

Now researchers of the Department of Medicine 1 led by Prof. Dr. Christoph Becker at Universitätsklinikum Erlangen have identified a molecule named cFlip which preserves the balance between cell death and regrowth. Messenger substances in the intestine constantly send the cells the signal ‘die’. In order to uphold the intestinal barrier, these signals must be monitored closely. The researchers were able to show that the molecule cFlip is crucial to keeping epithelial cells alive. cFlip blocks a molecule that plays a key role in cell death, preventing a state in which even small traces of cell death messenger substances in the intestine would lead to an activation of the suicide process in the cell. If the intestine is low on cFlip, too many epithelial cells in the intestinal mucosa die and leave the body open to attack from´bacteria.

‘Our results show how important strict regulation of cell death in intestinal epithelial cells is for the entire body, and emphasise the tremendous importance of these cells as the guardians of the organism,’ says Professor Becker. ‘We hope that our current work can offer a starting point for the treatment of intestinal diseases such as inflammatory diseases and bowel cancer.’

The researchers’ results were recently published in the renowned journal ‘Gastroenterology’.

Wittkopf N, Günther C, Martini E, He G, Amann K, He YW, Schuchmann M, Neurath MF, Becker C: Cellular FLICE-Like Inhibitory Protein Secures Intestinal Epithelial Cell Survival and Immune Homeostasis by Regulating Caspase-8. Gastroenterology, DOI: 10.1053/j.gastro.2013.08.059.

Information for the press:

Prof. Dr. Christoph Becker
Phone: +49 (0)9131 85 35886
christoph.becker@uk-erlangen.de

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