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We showed a new molecular mechanism that prevents the inflammatory bowel disease


The research team led by Dr. Philip X. Pimentel-Muiños in the Center for Cancer Research, the Institute of Molecular and Cellular Biology of Cancer (the CSIC-Universidad de Salamanca) (Spain) This document is only published in the journal Nature Communications. The studies were conducted in collaboration with the laboratory of Dr. Geert van Loo at the University of Ghent in Belgium.

Inflammatory bowel disease (primarily Crohn's disease and ulcerative colitis) sur & # 39; serious diseases arising from exposure to environmental factors on genetically susceptible individuals. About 5,000 new cases are diagnosed each year in Spain. These diseases are primarily anecdotal, but in the end, tend to develop into a chronic and refractory of the suras & # 39; serious complications that may require surgery. Symptomatic treatment is based on the introduction of anti-inflammatory and immunosuppressive agents, but there is no really curative therapy currently.

This lack of alternatives partly because of ignorance of the pathogenic mechanisms involved. Intestinal microenvironment with & # 39 is a unique physiological environment in which the epithelium must be sufficiently foresee all, to allow the absorption of nutrients, but also has to fend off a high bacterial load, which naturally colonizes the gastrointestinal tract. It is currently estimated that sporadic failures in the control of bacterial flora causing uncontrolled inflammatory response in genetically susceptible individuals, where defense mechanisms are not working normally. The mechanisms responsible for regulation of intestinal homeostasis very complicated and include several functional interaction of signaling pathways. What kind of molecules are involved and how they interact functionally with each other to control the bacterial flora and preventing the intestinal pathologies is not known clearly. It is hoped that a better understanding of these mechanisms contribute to the development of forms of prevention and truly effective therapy.

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Felipe Pimentel. (Photo: CIC)

In this work, the doctor Pimentel group, in collaboration with Dr. Van Loo, revealed that two unrelated protein (ATG16L1, involved in the regulation of cellular autophagy) and A20 (which is involved in controlling the inflammatory response), and physically interact mutually regulate their expression level and functional properties. This interaction is crucial for the prevention of inflammatory bowel disease as well as the absence or individual ATG16L1 A20 in intestinal epithelium causes no problems, but it causes the simultaneous removal of spontaneous strong inflammatory reaction associated with epithelial cell death and degeneration of the epithelium.

Laboratory-depth mechanistic implications of this interaction and concluded that the binding between the two proteins controls their expression level and the ability to regulate important cellular events such as cell autophagy pathways of inflammatory signaling, or the susceptibility of epithelial cells to cell death. "It ATG16L1 is especially important, as an activity that is described in this publication is in the region of the molecule (the area WD40), whose function is not clearly known," said Dr. Pimentel.

"Global MTA with & # 39 is the definition of a complete catalog of the molecular mechanisms regulating the homeostasis of the intestinal epithelium and dysfunction, which contributes to susceptibility to inflammatory bowel disease. Only a deep knowledge of these mechanisms may lead to truly effective therapeutic approach that can prevent and treat these diseases. "

The study was funded by the Ministry of Science and Innovation Universities, Junta de Castilla y León, the European Feder funds, the funds and programs Solorzano Broad Medical Research, the scientific program of the American Foundation "Broad Foundation / Crohn's and Colitis Foundation (CCF)", specializing in support research in inflammatory bowel disease. (Source: CIC / DICYT)

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