The MUC2 gene product: a human intestinal mucin

Allen, Adrian; Hutton, David A.; Pearson, Jeffrey P.

doi:10.1016/s1357-2725(98)00028-4

Cited by 175 publications

(164 citation statements)

References 14 publications

Supporting

Mentioning

157

Contrasting

Order By: Relevance

“…Goblet cells are specialized to secrete mucins, which contribute to the protective mucus gel barrier between the epithelium and the harsh environment of the lumen (32). Mucins are a family of highly O-glycosylated proteins, and mucin 2 (MUC2) is the most prominent protein secreted from goblet cells in the colon (33).…”

Section: Resultsmentioning

confidence: 99%

Negative feedback by IRE1β optimizes mucin production in goblet cells

Tsuru

Fujimoto

Takahashi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

141

144

View full text Add to dashboard Cite

In mammals, the prototypical endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1 (IRE1) has diverged into two paralogs. IRE1α is broadly expressed and mediates the unconventional splicing of X-box binding protein 1 (XBP1) mRNA during ER stress. By contrast, IRE1β is expressed selectively in the digestive tract, and its function remains unclear. Here, we report that IRE1β plays a distinctive role in mucin-secreting goblet cells. In IRE1β −/− mice, aberrant mucin 2 (MUC2) accumulated in the ER of goblet cells, accompanied by ER distension and elevated ER stress signaling such as increased XBP1 mRNA splicing. In contrast, conditional IRE1α −/− mice showed no such ER distension but a marked decrease in spliced XBP1 mRNA. mRNA stability assay revealed that MUC2 mRNA was greatly stabilized in IRE1β −/− mice. These findings suggest that in goblet cells, IRE1β, but not IRE1α, promotes efficient protein folding and secretion in the ER by optimizing the level of mRNA encoding their major secretory product, MUC2.inflammatory bowel disease | unfolded protein response

show abstract

Section: Resultsmentioning

confidence: 99%

Negative feedback by IRE1β optimizes mucin production in goblet cells

Tsuru

Fujimoto

Takahashi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

141

144

View full text Add to dashboard Cite

show abstract

“…For example, MUC2 is a goblet cell mucin predominantly expressed in the intestine. 29 Normal adult pancreas expresses MUC1 and MUC6, but not MUC2 and MUC5AC. MUC1 is expressed in the intercalated ductal cells 30 while MUC6 is exhibited in centroacinar cells.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic lymphoepithelial cysts express CEA and can contain mucous cells: potential pitfalls in the preoperative diagnosis

et al. 2010

View full text Add to dashboard Cite

Pancreatic lymphoepithelial cysts are rare benign cysts that cannot be reliably differentiated from neoplastic mucinous cysts preoperatively. Although elevated cyst fluid carcinoembryonic antigen (CEA) levels support a diagnosis of a mucinous cyst, the finding of increased CEA levels in lymphoepithelial cysts prompted this study. Nine resected lymphoepithelial cysts were examined for expression of CEA, carbohydrate antigen (CA) 19-9, CK7, p63, PAS-D and a panel of mucins. The pathology data were correlated with clinical information, including serum, cyst fluid and imaging studies. By computed tomography scan, although most lymphoepithelial cysts appeared cystic, 23% were described as masses. The endoscopic ultrasound findings were variable, but the lymphoepithelial cysts tended to be hypoechoic cystic lesions or masses. On cytology, 44% of the cysts had squamous cells, 67% had glandular cells and 56% had atypical cells. The cysts were resected because of size Z3 cm (89%), symptoms (44%) and/or elevated cyst fluid CEA levels (33%). The cyst fluid CEA levels in the three cysts tested were 4450 ng/ml. Histopathologically, all cysts were lined by mature, stratified squamous-type cells and produced keratin. Mucous cells were present in 78% of the cysts. The immunohistochemical profile of the squamous lining was CK7 þ , p63 þ , MUC1 þ , MUC4 þ , MUC2À, MUC5ACÀ and MUC6À. Even though lymphoepithelial cysts are lined by squamous-type epithelium, all our resected lymphoepithelial cysts expressed CEA and/or CA19-9, many contained mucous cells, and three exhibited markedly elevated cyst fluid CEA levels. Although cyst fluid CEA levels 4200 ng/ml support the diagnosis of mucinous neoplasms, this study emphasizes the need for clinicians and pathologists to recognize that lymphoepithelial cysts can mimic neoplastic mucinous cysts clinically, radiographically and on cyst fluid CEA analysis.

show abstract

“…Its promoter region was the first of the mucins to be elucidated (21). MUC2 is expressed primarily in the small intestine and colon of the GI tract (22), but its mRNA has also been detected in the airways of the lungs (23). However, there have been questions raised about how much MUC2 contributes to airway mucus secretion in normal and hypersecretory states.…”

Section: Muc2 Expression and Regulationmentioning

confidence: 99%

“…Studies of MUC2 in the GI tract and its expression during carcinogenesis reveal that promoter DNA methylation is a frequent mechanism that controls MUC2 expression (142,143). Previous data indicate that the sequence of the MUC2 promoter region approximately 343 bp upstream of the transcription start site contains elements regulating MUC2 expression (21,22). Recent results demonstrate that the methylation level of this region, comprising nine CpG sites, is related to MUC2 expression in colon cancer cells in vitro (143) and pancreatic cancer in vivo (142).…”

Section: Muc2: An Example Of An Epigenetically Controlled Mucin Genementioning

confidence: 99%

Regulation of Airway Mucin Gene Expression

Thai

Loukoianov

Wachi

et al. 2008

Annu. Rev. Physiol.

189

223

View full text Add to dashboard Cite

Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and airways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting airways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes.

show abstract

The MUC2 gene product: a human intestinal mucin

Cited by 175 publications

References 14 publications

Negative feedback by IRE1β optimizes mucin production in goblet cells

Negative feedback by IRE1β optimizes mucin production in goblet cells

Pancreatic lymphoepithelial cysts express CEA and can contain mucous cells: potential pitfalls in the preoperative diagnosis

Regulation of Airway Mucin Gene Expression

Contact Info

Product

Resources

About