Nasosinus mucin expression in normal and inflammatory conditions
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Abstract:
Purpose of review Mucin expression in normal nasosinus mucosa is upregulated in inflammatory conditions. However, as the first nine mucin genes are expressed, and as more mucins are expected to be expressed in nasosinus mucosa, the range and pattern of variations in mucin expression in nasosinus mucosa would be wide and complicated. This review discusses current knowledge on mucin expression in normal and pathologic nasosinus mucosa. Recent findings Studies on nasosinus mucin expression indicate that mucin genes upregulated in inflamed nasosinus mucosa include MUCs1, 2, 4, 5AC, 5B and 8 in different combinations and to various degrees. Nasosinus submucosal glands play a more important role in mucin expression than surface epithelium. However, most of the studies on nasosinus mucin expression are focused on basic science and as yet the clinical implications of nasosinus mucin gene expression are still unclear. Summary Nasosinus mucin expression is very complicated. Studies including large numbers of samples are needed to investigate the role of different physiological and pathological variables, including inflammatory mediators, in the control of nasosinus mucin expression. This is essential for better understanding of clinical implications of altered nasosinus mucin expression and for future therapeutic applications.Keywords:
Intestinal mucosa
Expression (computer science)
Mucin 2
Clostridial infection of the intestine can result in necrotic enteritis (NE), compromising production and health of poultry. Mucins play a major role in protecting the intestinal epithelium from infection. The relative roles of different mucins in gut pathology following bacterial challenge are unclear. This study was designed to quantify the expression of mucin and mucin-related genes, using intestinal samples from an NE challenge trial where birds were fed diets with or without in-feed antimicrobials. A method for quantifying mucin gene expression was established using a suite of reference genes to normalize expression data. This method was then used to quantify the expression of 11 candidate genes involved in mucin, inflammatory cytokine, or growth factor biosynthesis (IL-18, KGF, TLR4, TFF2, TNF-α, MUC2, MUC4, MUC5ac, MUC5b, MUC13, and MUC16). The only genes that were differentially expressed in the intestine among treatment groups were MUC2, MUC13, and MUC5ac. Expression of MUC2 and MUC13 was depressed by co-challenge with Eimeria spp. and Clostridium perfringens. Antimicrobial treatment prevented an NE-induced decrease in MUC2 expression but did not affect MUC13. The expression of MUC5ac was elevated in birds challenged with Eimeria spp./C. perfringens compared with unchallenged controls and antimicrobial treatment. Changes to MUC gene expression in challenged birds is most likely a consequence of severe necrosis of the jejunal mucosa.
Clostridium perfringens
Mucin 2
Intestinal mucosa
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Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium.
Citrobacter rodentium
Mucin 2
Intestinal mucosa
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Abstract Mucins are highly glycosylated proteins which protect the epithelium. In the small intestine, the goblet cell-secreted Muc2 mucin constitutes the main component of the loose mucus layer that traps luminal material. The transmembrane mucin Muc17 forms part of the carbohydrate-rich glycocalyx covering intestinal epithelial cells. Our study aimed at investigating the turnover of these mucins in the small intestine by using in vivo labeling of O -glycans with N -azidoacetylgalactosamine. Mice were injected intraperitoneally and sacrificed every hour up to 12 hours and at 24 hours. Samples were fixed with preservation of the mucus layer and stained for Muc2 and Muc17. Turnover of Muc2 was slower in goblet cells of the crypts compared to goblet cells along the villi. Muc17 showed stable expression over time at the plasma membrane on villi tips, in crypts and at crypt openings. In conclusion, we have identified different subtypes of goblet cells based on their rate of mucin biosynthesis and secretion. In order to protect the intestinal epithelium from chemical and bacterial hazards, fast and frequent renewal of the secreted mucus layer in the villi area is combined with massive secretion of stored Muc2 from goblet cells in the upper crypt.
Large intestine
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Background: Intestinal health of livestock and poultry is the basis of their body health. Different expression of growth factors is important cause of intestinal dysfunction, which further induced the illness of livestock and poultry. S-Methylmethionine Sulfonium Chloride (SMMSC) is also the main metabolite of methionine in animals. However, there are few studies exploring the relationship between SMMSC and intestinal epithelial growth factors. Methods: Piglet jejunal epithelial cells IPEC-J2 were treated with different concentrations of SMMSC at 0.1, 0.5 and 1 mM for 24 h respectively. Then real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were employed to detect the expression of Mucin-2 (MUC2), epidermal growth factor (EGF), transforming growth factor beta (TGF-β1), glucagon-like peptide-2 (GLP-2) and insulin-like growth factor-1 (IGF-1). Result: The results showed that 0.5 and 1 mM of SMMSC could stimulate the expression of MUC2, EGF, GLP-2 and IGF-1 while inhibit the expression of TGF-β1 in both mRNA and protein level (p less than 0.05). It is of great significance to repair intestinal mucosa injury, maintain intestinal mucosa barrier and promote intestinal development.
Mucin 2
Glucagon-like peptide-2
Intestinal mucosa
MUC1
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Abstract Recently, influence of bacteria colonization on development and maturation of gut wall is getting more into the focus of gastrointestinal research. For years, the main interest and research were aimed to the development and maturation of gut wall and its functional properties in normal conditions, less attention has been paid on the germ-free animals. Germ-free (GF) piglets have clear microbiological background and are reared in sterile environment. GF piglets are regarded as clinically relevant models for studying of human diseases, as these piglets’ manifest similar clinical symptoms to humans. In this study we briefly summarised the main characteristics in the distribution of goblet cells in the wall of jejunum and colon of GF piglets as healthy control (HC) group and piglets, which were experimentally infected by E. coli O149:K88 as ECK group. Neutral mucins were stained with periodic acid-Shiff (PAS) whereas acidic mucins are stained with Alcian blue. Numbers of goblet cells containing total acidic mucins in both, the jejunum and colon, differed significantly between HC and ECK piglets and in the colon, a similar trend was also observed. In the ECK piglets, jejunal goblet cells exhibited decrease in neutral mucins. This change in mucin profile in response to bacterial colonization suggests a potential role as a protective mechanism against pathogenic invasion of the intestinal mucosa during of gut mucosa development in piglets.
Goblet cell
Jejunum
Mucin 2
Intestinal mucosa
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Polyps are believed to be the source of mucus hypersecretion in chronic inflammation of the sinus. However, it is not clear which mucins are responsible for the hypersecretion of mucus by nasal polyps. We describe the over-expression of MUC8 mRNA in nasal polyps and the upregulation of MUC8 mRNA expression and downregulation of MUC5AC mRNA expression by inflammatory mediators. We found that the level of MUC8 mRNA, but not the level of MUC5AC mRNA, increased in nasal polyps. We also found that there was an increase in intracellular mucin in nasal polyps, compared to the normal nasal inferior turbinate. A mixture of inflammatory mediators increased MUC8 mRNA expression and decreased MUC5AC mRNA expression in cultured normal human nasal epithelial cells. Among inflammatory mediators, IL-4 is responsible for the decrease in MUC5AC mRNA and MUC5AC mucin secretion. These results indicate that MUC8 may be one of the major mucins secreted from the polyp epithelium and that it may play an important role in the pathogenesis of mucus hypersecretion in chronic sinusitis with polyps.
Nasal Polyps
Nasal glands
Pathogenesis
Mucin 2
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Abnormal expression patterns of mucin 2 (MUC2) have been reported in a variety of malignant tumors and precancerous lesions. Reduced MUC2 expression in the intestinal mucosa, caused by various pathogenic factors, is related to mechanical dysfunction of the intestinal mucosa barrier and increased intestinal mucosal permeability. However, the relationship between MUC2 and the intestinal mucosal barrier in patients with colorectal cancer (CRC) is not clear.To explore the relationship between MUC2 and intestinal mucosal barrier by characterizing the multiple expression patterns of MUC2 in CRC.Immunohistochemical staining was performed on intestinal tissue specimens from 100 CRC patients, including both cancer tissues and adjacent normal tissues. Enzyme-linked immunosorbent assays were performed on preoperative sera from 66 CRC patients and 20 normal sera to detect the serum levels of MUC2, diamine oxide (DAO), and D-lactate (D-LAC). The relationship between MUC2 expression and clinical parameters was calculated by the χ2 test or Fisher's exact test. Prognostic value of MUC2 was evaluated by Kaplan-Meier curve and log-rank tests.Immunohistochemical staining of 100 CRC tissues showed that the expression of MUC2 in cancer tissues was lower than that in normal tissues (54% vs 79%, P < 0.05), and it was correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis in CRC patients (P < 0.05). However, the serum level of MUC2 in CRC patients was higher than that in normal controls, and was positively associated with serum levels of human DAO (χ2 = 3.957, P < 0.05) and D-LAC (χ2 = 7.236, P < 0.05), which are the biomarkers of the functional status of the intestinal mucosal barrier. And the serum level of MUC2 was correlated with TNM stage, tumor type, and distant metastasis in CRC patients (P < 0.05). Kaplan-Meier curves showed that decreased MUC2 expression in CRC tissues predicted a poor survival.MUC2 in tissues may play a protective role by participating in the intestinal mucosal barrier and can be used as an indicator to evaluate the prognosis of CRC patients.
Mucin 2
Intestinal mucosa
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Mucin 2
Intestinal mucosa
Cysteine protease
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MUC2 and MUC3 are prominent mucin genes expressed in the human intestine. Using in situ hybridization with RNA probes, we examined the cellular distribution of MUC2 and MUC3 mRNA in normal, malignant, and inflammatory human intestinal tissues. In normal small intestine and colon, MUC2 mRNA was expressed exclusively in goblet cells and occurred throughout the entire height of the mucosa. MUC3 mRNA was expressed by goblet and columnar cells but was restricted to the villous compartment of the small intestine and the surface epithelium of the colon. Expression of MUC2 and MUC3 mRNA were both markedly decreased in poorly, moderately, and well-differentiated colon cancers but were preserved in mucinous colon cancers. In ulcerative colitis and Crohn's colitis tissues, MUC2 and MUC3 mRNA expression displayed a normal pattern regardless of whether the mucosa manifested active or quiescent inflammation. These findings indicate that MUC2 is goblet cell-specific, whereas MUC3 is related to maturation of intestinal epithelial cells. In colon cancers, the genetic regulation of MUC2 and MUC3 is different depending on the histological type of tumor. The constitutive expression of MUC2 and MUC3 mRNA in inflammatory bowel diseases suggests that these genes may be necessary for maintenance of normal epithelial cell function during inflammation.
Mucin 2
Goblet cell
Intestinal mucosa
Intestinal epithelium
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BACKGROUND
Crohn9s disease (CD) is a chronic relapsing inflammatory bowel disease of unknown origin. It is characterised by chronic mucosal ulcerations which affect any part of the intestine but most commonly are found in the ileum and proximal colon.AIMS
Studies were undertaken to provide information regarding cell specific expression of mucin genes in the ileum of patients with CD.PATIENTS AND METHODS
Expression of mucin genes was analysed in the ileal mucosa of patients with CD and controls by in situ hybridisation and immunohistochemistry.RESULTS
In healthy ileal mucosa, patients with CD showed a pattern identical to normal controls with main expression of MUC2 andMUC3, lesser expression ofMUC1 and MUC4, and no expression of MUC5AC,MUC5B, MUC6, orMUC7. In the involved mucosa, the pattern was somewhat comparable although heterogeneous to that observed in healthy ileal mucosa. Importantly, a particular mucin gene expression pattern was observed in ileal mucosa close to the ulcer margins in ulcer associated cell lineage, with the appearance ofMUC5AC and MUC6mRNAs and peptides, which are normally restricted to the stomach (MUC5AC and MUC6) and duodenum (MUC6), and disappearance ofMUC2.CONCLUSIONS
Our results suggest that gel forming mucins (more particularly MUC5AC and MUC6) may have a role in epithelial wound healing after mucosal injury in inflammatory bowel diseases in addition to mucosal protection.MUC1
Intestinal mucosa
Mucin 2
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