Intestinal Goblet Cells and Mucins in Health and Disease: Recent Insights and Progress

By Y. S. Kim, S. Ho. Current Gastroenterology Reports, 2010

1,369 citations recorded by the source corpus.

The mucus layer coating the gastrointestinal tract is the front line of innate host defense, largely because of the secretory products of intestinal goblet cells. Goblet cells synthesize secretory mucin glycoproteins (MUC2) and bioactive molecules such as epithelial membrane-bound mucins (MUC1, MUC3, MUC17), trefoil factor peptides (TFF), resistin-like molecule β (RELMβ), and Fc-γ binding protein (Fcgbp). The MUC2 mucin protein forms trimers by disulfide bonding in cysteine-rich amino terminal von Willebrand factor (vWF) domains, coupled with crosslinking provided by TFF and Fcgbp proteins with MUC2 vWF domains, resulting in a highly viscous extracellular layer. Colonization by commensal intestinal microbiota is limited to an outer “loose” mucus layer, and interacts with the diverse oligosaccharides of mucin glycoproteins, whereas an “inner” adherent mucus layer is largely devoid of bacteria. Defective mucus layers resulting from lack of MUC2 mucin, mutated Muc2 mucin vWF domains, or from deletion of core mucin glycosyltransferase enzymes in mice result in increased bacterial adhesion to the surface epithelium, increased intestinal permeability, and enhanced susceptibility to colitis caused by dextran sodium sulfate. Changes in mucin gene expression and mucin glycan structures occur in cancers of the intestine, contributing to diverse biologic properties involved in the development and progression of cancer. Further research is needed on identification and functional significance of various components of mucus layers and the complex interactions among mucus layers, microbiota, epithelial cells, and the underlying innate and adaptive immunity. Further elucidation of the regulatory mechanisms involved in mucin changes in cancer and inflammation may lead to the development of novel therapeutic approaches.

Subfields: Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/1e64c22825f98c3da3d030355ae9ae6b8fd47f40

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In Molecular Biology

1. H. Smidt
2. Herbert Tilg
3. M. Conlon
4. S. Bischoff
5. D. Haller
6. A. Bird
7. J. Gerritsen
8. Ger T. Rijkers

In Surgery

1. S. Bischoff
2. Herbert Tilg
3. W. D. de Vos

Citations in the corpus

• The Impact of Diet and Lifestyle on Gut Microbiota and Human Health (2014, background): “A layer of mucus, produced by goblet cells, lines the epithelium of the GI tract and acts as a barrier to microbial invasion of tissues and can contribute to intestinal homeostasis [131,132].”
• A guide to histomorphological evaluation of intestinal inflammation in mouse models. (2014, background): “4573 Int J Clin Exp Pathol 2014;7(8):4557-4576 cells are reduced in number and size and it is still unknown whether the alterations in mucin production contribute to the initiation or result from the inflammation [38].”
• Intestinal permeability – a new target for disease prevention and therapy (2014, background): “These are also glycosylated and are released upon binding by microorganisms as a defense mechanism to prevent colonization [29,30].”
• Intestinal microbiota in human health and disease: the impact of probiotics (2011, background): “It has been demonstrated in rodents that intestinal microorganisms are able to survive and even proliferate in the outer loose mucus layer since the glycans present in this layer are accessible as energy source for these microorganisms (Kim and Ho 2010; Johansson et al. 2010).”
• Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent (2013, background): “Mucus is continuously secreted into the GIT lumen by specialized epithelial cells, the goblet cells, and is mainly composed of heavily O-glycosylated proteins called mucins [9].”
• Pathological bacterial translocation in liver cirrhosis. (2014, background): “MUC2 is the major secretory mucin being stimulated by a wide array of bioactive factors including microbes/-products, and inflammatory cytokines [57].”