Disease relevance of Muc2

• Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis [1].
• In a mouse model of human cystic fibrosis, both soluble Muc3 and goblet cell Muc2 were increased in amount and hypersecreted [2].
• The tumor that arose in the transplant site from this nodule was a well-differentiated adenocarcinoma with mucin production [3].
• Mucin histochemistry by paradoxical concanavalin A staining in experimental gastric cancers induced in Wistar rats by N-methyl-N-nitro-N-nitrosoguanidine or 4-nitroquinoline 1-oxide [4].
• Resolution of edema, mucin repletion, thickening of muscularis mucosa and propria, and fibrosis were observed at 3 weeks [5].

Psychiatry related information on Muc2

• PAS staining revealed that DMH treatment lowered mucin secretion in crypts, which was substantially lowered by food deprivation [6].

High impact information on Muc2

• After MNNG treatment, class III mucin-positive pyloric glands with a low Pg 1 content in normal-looking pyloric mucosa were found from week 10; subsequently, their number increased with time [7].
• Histologic examination showed that unlike adenocarcinomas with high mucin-producing activity, which were common in rats on pellet diet, most of the adenocarcinomas that developed in rats fed on defined diet were highly or well differentiated, with a typical glandular pattern [8].
• All of these sublines contained a large mucin-type sialoglycoprotein (ASGP-1) as a major cell surface component [9].
• The disappearance of nitrite from buffer was little affected by the addition of pepsin, mucin, albumin, or rat gastric contents [10].
• Adaptation was not associated with any significant change in basal gastric acid secretion in monkeys and occurred despite a significant decrease in gastric mucin in rats [11].

Chemical compound and disease context of Muc2

• The adenocarcinomas that did develop in rats treated with the higher dose of tetragastrin had high mucin-producing activity and showed little or no typical glandular structure [12].
• Molecular cloning and sequencing of the mucin subunit of a heterodimeric, bifunctional cell surface glycoprotein complex of ascites rat mammary adenocarcinoma cells [13].
• Platelet-activating factor induces goblet cell hyperplasia and mucin gene expression in airways [14].
• Role of the putative "link" glycopeptide of intestinal mucin in binding of piliated Escherichia coli serotype O157:H7 strain CL-49 [15].
• Histologically, the adenocarcinomas that did develop in rats treated with cysteamine exhibited high mucin-producing activity [16].

Biological context of Muc2

• The glycosylation of rat intestinal Muc2 mucin varies between rat strains and the small and large intestine. A study of O-linked oligosaccharides by a mass spectrometric approach [17].
• It is concluded that the intact cystine-knot domain is essential for dimerization of the C-terminal domain of rat Muc2, and that residue Cys-X in the knot plays a key role [18].
• No methotrexate-induced changes were seen in epithelial morphology, proliferation, apoptosis, Muc2, and TFF3 immunostaining in the colon [19].
• The maintenance or upregulation of Muc2 and TFF3 synthesis and secretion levels implies that goblet cells at least maintain their epithelial defense and repair capacity during acute inflammation induced by DSS [20].
• N-Ethylmaleimide, a known inhibitor of cytoprotection by cysteamine, had no effect on mucin secretion [21].

Anatomical context of Muc2

• The C-terminal domain of rat Muc2 (RMC), a truncated RMC mutant containing the CK, and mutants lacking N9 and N10 sites, were expressed in COS-1 cells and the products monitored by radioactive [(35)S]Met/Cys metabolic pulse-chase and immunoprecipitation [22].
• The expression of the rat Muc2 in the large intestine was confirmed immunochemically and by Northern blotting [17].
• This study demonstrated that tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine in mucoid effusion, markedly increased Muc2 mucin mRNA expression in middle ear epithelium, in a time- and dose-dependent manner [23].
• RESULTS: the Muc2 mucin gene was expressed in middle ear mucosa of the control rats [24].
• In the Eustachian tube, the Muc2, Muc4 and Muc5 mucin genes were expressed in both control and pneumococcal inoculation groups [24].

Associations of Muc2 with chemical compounds

• We conclude that under normal conditions the presence of the N9 glycan functions to maintain a folding rate for mucin monomers that is sufficiently slow to allow structural maturation and stability of Muc2 dimers [22].
• Even after purification, however, the mucin was still vulnerable to partial proteolysis unless it was stored in guanidinium chloride at -20 degrees C. These findings imply that a potent proteinase contaminant remains tightly bound to the mucin through every step of purification, or else that the mucin has autocatalytic properties [25].
• Previous studies indicate that in addition to an unpaired cysteine, the three intramolecular cystine bonds of the knot are important for stability of the dimers formed by rat intestinal mucin Muc2 [22].
• N-linked oligosaccharides play a role in disulphide-dependent dimerization of intestinal mucin Muc2 [22].
• We propose that the presence, on the surface of M cells, of carbohydrates also expressed on Muc2, together with the absence of an enterocyte-associated mucin, could favor pathogen attachment and accessibility to the M-cell luminal membrane [26].

Physical interactions of Muc2

• Muc4/sialomucin complex (SMC) is a heterodimeric glycoprotein complex derived from a single gene that is post-translationally processed into mucin (ASGP-1) and transmembrane (ASGP-2) subunits [27].
• The ED50 for vasoactive intestinal peptide-stimulated mucin release was 0.12 +/- 0.05 nM, thus suggesting an activation anomaly in the vasoactive intestinal peptide receptor-coupled signal transduction pathway at a point between cyclic AMP production and mucin release [28].

Regulatory relationships of Muc2

• Src kinase-dependent epidermal growth factor receptor transactivation in PPARgamma ligand-induced suppression of Porphyromonas gingivalis interference with salivary mucin synthesis [29].
• Here we report on the role of ET-1 in the mediation of the detrimental influence of Helicobacter pylori on the synthesis of gastric mucin [30].
• Inhibition of ERK with PD98059 accelerated (up to 36.1%) the LPS-induced decrease in mucin synthesis, and caused further enhancement in caspase-3 activity and apoptosis [31].
• IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils [32].
• Leptin suppresses Porphyromonas gingivalis lipopolysaccharide interference with salivary mucin synthesis [33].

Other interactions of Muc2

• Unlike the C-terminus of Muc2 and many secretory mucins, Muc3 contains two EGF motifs and a putative transmembrane domain [34].
• The enhanced expression of cytoprotective molecules (Muc2, TFF3, lysozyme) during damage represents maintenance of goblet cell and Paneth cell functions, most likely to protect the epithelium [35].
• The cationic C-terminus of rat Muc2 facilitates dimer formation post translationally and is subsequently removed by furin [36].
• Mucin-1 (Muc1), an integral membrane mucin, is expressed on the apical surface of uterine epithelial cells (UE) of various species [37].
• Up-regulation in endothelin-1 by Helicobacter pylori lipopolysaccharide interferes with gastric mucin synthesis via epidermal growth factor receptor transactivation [30].

Analytical, diagnostic and therapeutic context of Muc2

• DNA constructs based on the 534-amino-acid C-terminus of rat mucin protein Muc2 (RMC), were transfected into COS cells and the resultant (35)S-labelled dimers and monomers were detected by SDS/PAGE of immunoprecipitates [18].
• After infusion of vasoactive intestinal polypeptide the secretory cells, which in the control group were rich in PAS-positive mucin, became almost completely PAS-negative [38].
• Mucin (tissue content and secretion) was measured using a highly specific enzyme-linked immunoassay [39].
• The purpose of this study was to measure the release of mucin glycoproteins from rat stomach after treatment with cysteamine and prostaglandin F2 beta, two structurally unrelated drugs that have been shown to protect the stomach against the noxious effects of alcohol and other damaging agents [21].
• We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E2 secretion, and colonic mast cell activation, as well as increased colonic motility [40].

References