Colonic gene expression patterns of mucin muc2 knockout mice reveal various phases in colitis development1

Lü, Peng; Paassen, Nanda Burger‐van; Sluis, Maria van der; Witte-Bouma, Janneke; Kerckaert, Jean‐Pierre; Goudoever, Johannes B. van; Seuningen, Isabelle Van; Renes, Ingrid B.

doi:10.1002/ibd.21592

Cited by 43 publications

(31 citation statements)

References 41 publications

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“…4,5 This is associated with exacerbation of inflammatory gene expression and a decline in regulatory T cells. 6 In the ileum, the interleukin (IL)-22 regulated network Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).…”

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confidence: 99%

Identification of Commensal Species Positively Correlated with Early Stress Responses to a Compromised Mucus Barrier

Sovran

Lü

Loonen

et al. 2016

Inflammatory Bowel Diseases

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confidence: 99%

Identification of Commensal Species Positively Correlated with Early Stress Responses to a Compromised Mucus Barrier

Sovran

Lü

Loonen

et al. 2016

Inflammatory Bowel Diseases

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“…not seen experimentally with deglycosylated MUC2 glycoprotein. Muc2-knockout mice have increased susceptibility to intestinal pathogens [27], active inflammation by 2-4 weeks of age and altered expression in tight junction-related genes [28], but there is no evidence to date of any underlying defect in MUC2 synthesis in human IBD.…”

Section: Alterations In the Mucosal Barrier In Inflammatory Bowel Dismentioning

confidence: 99%

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Merga

Campbell

Rhodes

2014

Dig Dis

157

113

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The mucosal barrier has three major components, the mucus layer, the epithelial glycocalyx and the surface epithelium itself, whose integrity largely depends on tight junction function. In health, there is relatively little direct interaction between the luminal microbiota and the epithelium - the continuous mucus layer in the colon keeps the surface epithelium out of contact with bacteria and the ileo-caecal valve ensures that the distal small intestine is relatively microbe free. Most interaction takes place at the Peyer's patches in the distal ileum and their smaller colonic equivalents, the lymphoid follicles. Peyer's patches are overlain by a ‘dome' epithelium, 5% of whose cells are specialised M (microfold) epithelial cells, which act as the major portal of entry for bacteria. There are no goblet cells in the dome epithelium and M cells have a very sparse glycocalyx allowing easy microbial interaction. It is intriguing that the typical age range for the onset of Crohn's disease (CD) is similar to the age at which the number of Peyer's patches is greatest. Peyer's patches are commonly the sites of the initial lesions in CD and the ‘anti-pancreatic' antibody associated with CD has been shown to have as its epitope the glycoprotein 2 that is the receptor for type-1 bacterial fimbrial protein (fimH) on M cells. There are many reasons to believe that the mucosal barrier is critically important in the pathogenesis of inflammatory bowel disease (IBD). These include (i) associations between both CD and ulcerative colitis (UC) with genes that are relevant to the mucosal barrier; (ii) increased intestinal permeability in unaffected relatives of CD patients; (iii) increased immune reactivity against bacterial antigens, and (iv) animal models in which altered mucosal barrier, e.g. denudation of the mucus layer associated with oral dextran sulphate in rodents, induces colitis. Whilst some IBD patients may have genetic factors leading to weakening of the mucosal barrier, it is likely that environmental factors may be even more important. Some may be subtle and indirect, e.g. the effects of stress on the mucosa barrier, whilst others may be more obvious, e.g. the effect of pathogen-related gastroenteritis, known often to act as trigger for IBD relapse. We have also been very interested in the potentially harmful effects of ingested detergents - either by contamination of cutlery by inadequate rinsing or via ingestion of processed foods containing permitted emulsifiers. In vitro and ex vivo studies show that even very small trace amounts of these surfactants can greatly increase bacterial translocation. Implications for therapy are not yet so obvious. We advise our IBD patients to avoid processed foods containing emulsifiers and to rinse their dishes well - whilst accepting that there is no direct evidence yet to support this. Therapies that aim to enhance the mucosal barrier have yet to come to market, but trials of enteric-delivered phosphatidylcholine in UC are promising. The faecal concentration of mucus-degrading bact...

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“…Additionally, microarray analysis on 2–4-week-old Muc2 −/− mice following colitis development revealed upregulation of genes involved in various immunological processes including the following: antigen processing/presentation, B cell receptor- and T cell receptor-mediated signal transduction, and Jak-STAT signaling (Fig. 3b) [62]. These mice expressed elevated levels of immunoglobulins, pro-inflammatory cytokines, chemokines, and antimicrobial proteins.…”

Section: Utilization Of Mucin Mouse Models For Studying Pathologicamentioning

confidence: 99%

“…These mice expressed elevated levels of immunoglobulins, pro-inflammatory cytokines, chemokines, and antimicrobial proteins. Moreover, 4-week-old Muc2 −/− mice showed significant alteration in the expression of certain cell structure maintenance genes, including upregulation of claudin-10 and downregulation of claudin-1 and claudin-5 [62]. …”

Section: Utilization Of Mucin Mouse Models For Studying Pathologicamentioning

confidence: 99%

Genetically engineered mucin mouse models for inflammation and cancer

Joshi

Kumar

Bafna

et al. 2015

Cancer Metastasis Rev

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Mucins are heavily O-glycosylated proteins primarily produced by glandular and ductal epithelial cells, either in membrane-tethered or secretory forms, for providing lubrication and protection from various exogenous and endogenous insults. However, recent studies have linked their aberrant overexpression with infection, inflammation, and cancer that underscores their importance in tissue homeostasis. In this review, we present current status of the existing mouse models that have been developed to gain insights into the functional role(s) of mucins under physiological and pathological conditions. Knockout mouse models for membrane-associated (Muc1 and Muc16) and secretory mucins (Muc2) have helped us to elucidate the role of mucins in providing effective and protective barrier functions against pathological threats, participation in disease progression, and improved our understanding of mucin interaction with biotic and abiotic environmental components. Emphasis is also given to available transgenic mouse models (MUC1 and MUC7), which has been exploited to understand the context-dependent regulation and therapeutic potential of human mucins during inflammation and cancer.

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Colonic gene expression patterns of mucin muc2 knockout mice reveal various phases in colitis development1

Cited by 43 publications

References 41 publications

Identification of Commensal Species Positively Correlated with Early Stress Responses to a Compromised Mucus Barrier

Identification of Commensal Species Positively Correlated with Early Stress Responses to a Compromised Mucus Barrier

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Genetically engineered mucin mouse models for inflammation and cancer

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