The MUC13 cell-surface mucin protects against intestinal inflammation by inhibiting epithelial cell apoptosis

Sheng, Yonghua; Lourie, Rohan; Lindén, Sara K.; Jeffery, Penny L.; Roche, Deborah; Tran, Tri; Png, Chin Wen; Waterhouse, Nigel J.; Sutton, Philip; Florin, Timothy H.; McGuckin, Michael A.

doi:10.1136/gut.2011.239194

Cited by 107 publications

(83 citation statements)

References 39 publications

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“…Linking mucins, inflammation, and colitis, mucins are involved in the regulation of apoptosis and cell proliferation in different regions of the gastrointestinal tract. A MUC13 knockout mouse displays increased intestinal inflammation in the mouse colitis model with dextran sulfate [83]. This study nicely uncovers a role for MUC13 in inhibiting apoptosis, as the increased intestinal inflammation observed in the MUC13 knockout mice is most likely caused by increased apoptosis of intestinal epithelial cells.…”

Section: Barrier Function Mucosal Maintenance and Interactions Withmentioning

confidence: 78%

Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer

Putten¹,

Strijbis²

2017

J Innate Immun

206

213

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Mucosal surfaces line our body cavities and provide the interaction surface between commensal and pathogenic microbiota and the host. The barrier function of the mucosal layer is largely maintained by gel-forming mucin proteins that are secreted by goblet cells. In addition, mucosal epithelial cells express cell-bound mucins that have both barrier and signaling functions. The family of transmembrane mucins consists of diverse members that share a few characteristics. The highly glycosylated extracellular mucin domains inhibit invasion by pathogenic bacteria and can form a tight mesh structure that protects cells in harmful conditions. The intracellular tails of transmembrane mucins can be phosphorylated and connect to signaling pathways that regulate inflammation, cell-cell interactions, differentiation, and apoptosis. Transmembrane mucins play important roles in preventing infection at mucosal surfaces, but are also renowned for their contributions to the development, progression, and metastasis of adenocarcinomas. In general, transmembrane mucins seem to have evolved to monitor and repair damaged epithelia, but these functions can be highjacked by cancer cells to yield a survival advantage. This review presents an overview of the current knowledge of the functions of transmembrane mucins in inflammatory processes and carcinogenesis in order to better understand the diverse functions of these multifunctional proteins.

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Section: Barrier Function Mucosal Maintenance and Interactions Withmentioning

confidence: 78%

Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer

Putten¹,

Strijbis²

2017

J Innate Immun

206

213

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“…The transmembrane mucin Muc13 is not expressed in a healthy stom-ach. Under healthy conditions, this cell surface mucin is mainly expressed in the glycocalyx of enterocytes and goblet cells in the small and large intestine, particularly at the luminal surface (21). Interestingly, the mRNA expression of Muc13 was significantly increased from day 1 until 9 weeks postinfection (P Ͻ 0.001) in the fundus of the stomach of both H. heilmannii-and H. pylori-infected mice compared to its mRNA expression in the control group (fold change for ASB1, 6.08 Ϯ 0.84, and for SS1, 5.91 Ϯ 1.21) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The expression level of Muc13 remained upregulated until 52 weeks postinfection. It has been described that sustained elevation of the expression of cell surface mucins may promote the transition from chronic inflammation to cancer (21). How Muc13 influences the Helicobacter colonization process is unknown and needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…MUC13 has been shown to be highly expressed in human gastric cancer (21), but increased mRNA expression of it in the early stages of Helicobacter colonization has so far never been described. The positive correlation found between the increased Muc13 expression and the increased number of Helicobacter bacteria in the fundus of the stomach during the first 9 weeks of infection suggests a potential role for Muc13 in Helicobacter colonization.…”

Section: Discussionmentioning

confidence: 99%

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Gastric De Novo Muc13 Expression and Spasmolytic Polypeptide-Expressing Metaplasia during Helicobacter heilmannii Infection

et al. 2014

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bHelicobacter heilmannii is a zoonotic bacterium that has been associated with gastric disease in humans. In this study, the mRNA expression of mucins in the stomach of BALB/c mice was analyzed at several time points during a 1-year infection with this bacterium, during which gastric disease progressed in severity. Markers for acid production by parietal cells and mucous metaplasia were also examined. In the first 9 weeks postinfection, the mRNA expression of Muc6 was clearly upregulated in both the antrum and fundus of the stomach of H. heilmannii-infected mice. Interestingly, Muc13 was upregulated already at 1 day postinfection in the fundus of the stomach. Its expression level remained high in the stomach over the course of the infection. This mucin is, however, not expressed in a healthy stomach, and high expression of this mucin has so far only been described in gastric cancer. In the later stages of infection, mRNA expression of H ؉ /K ؉ -ATPase ␣/␤ and KCNQ1 decreased, whereas the expression of Muc4, Tff2, Dmbt1, and polymeric immunoglobulin receptor (pIgR) increased starting at 16 weeks postinfection onwards, suggesting the existence of spasmolytic polypeptide-expressing metaplasia in the fundus of the stomach. Mucous metaplasia present in the mucosa surrounding low-grade mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions was also histologically confirmed. Our findings indicate that H. heilmannii infection causes severe gastric pathologies and alterations in the expression pattern of gastric mucins, such as Muc6 and Muc13, as well as disrupting gastric homeostasis by inducing the loss of parietal cells, resulting in the development of mucous metaplasia.

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“…27,44,45 Similarly, mice deficient in muc13 or core 3 ß1,3-N-acetylglucosaminyl-transferase (C3GnT) with therefore a reduced mucin O-glycosylation exhibit an enhanced susceptibility to inflammation. 46,47 Also, aberrant mucin assembly-associated ER stress in goblet and Paneth cells was reported in 2 strains of muc2 mutant mice leading to spontaneous inflammation and increased mucosal permeability. 48 Altered mucin expression and reduced antimicrobial peptide expression has also been observed in patients with ileal Crohn's disease or ulcerative colitis.…”

mentioning

confidence: 99%

Antimicrobial peptides and the enteric mucus layer act in concert to protect the intestinal mucosa

Dupont¹,

et al. 2014

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The MUC13 cell-surface mucin protects against intestinal inflammation by inhibiting epithelial cell apoptosis

Abstract: These novel findings indicate a protective role for Muc13 in the colonic epithelium by inhibiting toxin-induced apoptosis and have important implications for intestinal infections, inflammatory diseases and the development of intestinal cancer.

Cited by 107 publications

References 39 publications

Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer

Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer

Gastric De Novo Muc13 Expression and Spasmolytic Polypeptide-Expressing Metaplasia during Helicobacter heilmannii Infection

Antimicrobial peptides and the enteric mucus layer act in concert to protect the intestinal mucosa

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