Mucin Muc2 deficiency and weaning influences the expression of the innate defense genes Reg3β, Reg3γ and angiogenin-4.

Background: Mucin Muc2 is the structural component of the intestinal mucus layer. Absence of Muc2 leads to loss of this layer allowing direct bacterial-epithelial interactions. We hypothesized that absence of the mucus layer leads to increased expression of innate defense peptides.

Colonic gene expression patterns of mucin Muc2 knockout mice reveal various phases in colitis development.

Background: Mucin Muc2 knockout (Muc2(-/-)) mice spontaneously develop colitis.

Methods: To identify genes and biological responses which play a pivotal role during colitis development in Muc2(-/-) mice, gene expression profiles of colonic tissues from 2- and 4-week-old Muc2(-/-) and wildtype mice were determined using microarrays.

Results: The majority of highly upregulated genes in 2-week-old as well as 4-week-old Muc2(-/-) mice were primarily involved in immune responses related to antigen processing/presentation, B-cell and T-cell receptor signaling, leukocyte transendothelial migration, and Jak-STAT signaling.

Colitis development during the suckling-weaning transition in mucin Muc2-deficient mice.

The mucin Muc2 is the structural component of the colonic mucus layer. Adult Muc2 knockout (Muc2(-/-)) mice suffer from severe colitis. We hypothesized that Muc2 deficiency induces inflammation before weaning of mother's milk [postnatal day (P) 14] with aggravation of colitis after weaning (P28).

EuropeaN Energy balance Research to prevent excessive weight Gain among Youth (ENERGY) project: Design and methodology of the ENERGY cross-sectional survey.

Background: Obesity treatment is by large ineffective long term, and more emphasis on the prevention of excessive weight gain in childhood and adolescence is warranted. To inform energy balance related behaviour (EBRB) change interventions, insight in the potential personal, family and school environmental correlates of these behaviours is needed. Studies on such multilevel correlates of EBRB among schoolchildren in Europe are lacking.

Longitudinal associations of energy balance-related behaviours and cross-sectional associations of clusters and body mass index in Norwegian adolescents.

Background: Insight into the role of energy balance-related behaviours (EBRB) is of great importance when it comes to prevention of weight gain and design of interventions tailored to target these behaviours.

Objectives: First, the present study examines the longitudinal association of four EBRB in Norwegian adolescents. Second, it aims to examine whether clusters of EBRB are cross-sectionally associated with being overweight.

Threonine metabolism in the intestine of mice: loss of mucin 2 induces the threonine catabolic pathway.

Objectives: Previous studies have shown that the intestine uses a major part of the dietary threonine intake for the synthesis of the structural component of the protective intestinal mucus layer, the secretory mucin Muc2. In this context, the high intestinal demand for dietary threonine probably results from its incorporation into secretory mucins rich in threonine residues. Therefore, we compared threonine utilization in the colon of Muc2 knockout (Muc2-/-) and wild-type (Muc2+/+) mice to investigate the intestinal dietary threonine metabolism in the absence of Muc2, which results in inflammation of the colon.

The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection.

SCFAs (short-chain fatty acids), fermentation products of bacteria, influence epithelial-specific gene expression. We hypothesize that SCFAs affect goblet-cell-specific mucin MUC2 expression and thereby alter epithelial protection. In the present study, our aim was to investigate the mechanisms that regulate butyrate-mediated effects on MUC2 synthesis.

Combined defects in epithelial and immunoregulatory factors exacerbate the pathogenesis of inflammation: mucin 2-interleukin 10-deficient mice.

Expression of the mucin MUC2, the structural component of the colonic mucus layer, is lowered in ulcerative colitis. Furthermore, interleukin (IL)-10 knockout (IL-10-/-) mice develop colitis and have reduced Muc2 levels. Our aim was to obtain insight into the role of Muc2 and IL-10 in epithelial protection.

Forkhead box transcription factors Foxa1 and Foxa2 are important regulators of Muc2 mucin expression in intestinal epithelial cells.

The mucin Muc2 is the main component of the intestinal mucus layer and thus plays important roles in intestinal protection. Therefore, it is important to understand its regulation during goblet cell differentiation. Foxa1 and Foxa2 forkhead box transcription factors (TFs) participate in transcriptional programs governing intestinal cell differentiation.

Methotrexate-induced mucositis in mucin 2-deficient mice.

The mucin Muc2 or Mycin2 (Muc2), which is the main structural component of the protective mucus layer, has shown to be upregulated during chemotherapy-induced mucositis. As Muc2 has shown to have protective capacities, upregulation of Muc2 may be a counter reaction of the intestine protecting against mucositis. Therefore, increasing Muc2 protein levels could be a therapeutic target in mucositis prevention or reduction.

Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection.

Background & Aims: Expression of mucin MUC2, the structural component of the colonic mucus layer, is lowered in inflammatory bowel disease. Our aim was to obtain insight in the role of Muc2 in epithelial protection.

Methods: Muc2 knockout (Muc2(-/-)) and Muc2 heterozygous (Muc2(+/-)) mice were characterized and challenged by a colitis-inducing agent, dextran sulfate sodium (DSS).

Contributions of mucosal immune cells to methotrexate-induced mucositis.

The use of high doses of the anti-cancer drug methotrexate (MTX) is associated with intestinal damage. As a result, mucosal immune cells become increasingly exposed to a vast amount of microbial stimuli. We aimed at determining whether these cells are still functional during MTX treatment.

Interleukin 10-deficient mice exhibit defective colonic Muc2 synthesis before and after induction of colitis by commensal bacteria.

Germ-free (GF) interleukin 10-deficient (IL-10) mice develop chronic colitis after colonization by normal enteric bacteria. Muc2 is the major structural component of the protective colonic mucus. Our aim was to determine whether primary or induced aberrations in Muc2 synthesis occur in GF IL-10 mice that develop colitis after bacterial colonization.

The murine Muc2 mucin gene is transcriptionally regulated by the zinc-finger GATA-4 transcription factor in intestinal cells.

MUC2, the major mucin in the intestine, is expressed early during development and shows an altered expression pattern in intestinal bowel diseases. However, the mechanisms responsible for MUC2 expression in the intestine during these events are largely unknown. Having found putative GATA binding sites in the murine Muc2 promoter and that GATA-4 is expressed in Muc2-expressing goblet cells of the mouse small intestine, we undertook to study its regulation by this transcription factor.

Transcriptional activation of the murine Muc5ac mucin gene in epithelial cancer cells by TGF-beta/Smad4 signalling pathway is potentiated by Sp1.

The nucleotide sequence of the pMS1 clone was submitted to the GenBank Nucleotide Sequence Database under accession number AF288076. Changes in the expression of mucin genes in gastrointestinal cancers is thought to contribute to the development of the disease. In our laboratory we have shown previously that MUC5AC is aberrantly expressed in rectosigmoid villous adenomas.

Role of mucins in inflammatory bowel disease: important lessons from experimental models.

Inflammatory bowel disease (IBD) is characterized by a chronically inflamed mucosa of the gastrointestinal tract, caused by an underlying immune imbalance and triggered by luminal substances, including bacteria. Mucus forms a gel layer covering the gastrointestinal tract, acting as a semi-permeable barrier between the lumen and the epithelium. Mucins, the building blocks of the mucus gel, determine the thickness and properties of mucus.