Our key interest is to understand the complex protective system of the gut with a specific focus on the secreted mucus and its role in protection and health. The epithelium of the intestinal tract is constantly challenged by ingested harsh and sometimes infectious material, endogenously produced dangerous compounds as high concentrations of acid or bicarbonate, digestive enzymes and bile. In addition our gut is the preferred home for numerous bacteria, our gut microbiota. Our relationship with the microbes is mutualistic and a balanced coexistence has developed over extensive evolutionary time. We believe that secreted mucus is of importance for protection with regards to all these aspects. The intestinal mucus aids in compartmentalization in different ways throughout the intestine. In the small intestine it functions as a diffusion barrier which will be enriched in secreted molecules as microbial defense proteins and peptides. In the large intestine the mucus forms a dense layer keeping most bacteria at a distance from the epithelium.
Mucus in colitis
Mucus defects are closely linked to colitis. Failure of the mucus to keep bacteria at distance from the epithelium is observed in animal models genetically of chemically manipulated to develop colitis and in patients suffering from ulcerative colitis. A defect mucus barrier could be a result of various problems relating to structural organization, rate of production and secretion or alterations in the surrounding environment. A key question that we want to understand is how the mucus develops and what wat can cause its defects. Mucus production, secretion, processing, epithelial ion transport, pH, cell proliferation and effects of immune modulators are all important for a functional mucus barrier.
Molecular functions in the mucus
Several components build up mucus with the highly O-glycosylated, oligomeric MUC2 mucin as the structural frame. We termed molecules produced and secreted by the goblet cells as core mucus proteins. Most of these proteins have fairly unknown functions. Among these proteins we are studying FCGBP, a likely structural component in the mucus composed of repeated vWD domains, and CLCA1, a metalloprotease important for mucus processing and transformation of the mucus structure.
The goblet cells
The mucus is secreted by very specialized secretory cells called goblet cells due to their shape. Goblet cells develop from the crypt located stem cells through transcriptionally controlled events, and our single cell data of sorted goblet cells revile several distinct populations of goblet cells. We are now studying the functions of specific clusters of goblet cells in both mice and humans in the context of colitis. The mucus biosynthesis machinery is also very demanding for the cell and several molecules involved are goblet cell specific. Mucus secretion is also occurs trough different mechanisms. We aim to get a better understanding of different goblet cells and their role in forming the protective mucus.
More about the Sahlgrenska Academy Mucin Biology Group
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