Dynamic regulation of mucus gel thickness in rat duodenum

Akiba, Yasutada; Guth, Paul H.; Engel, Eli; Nastaskin, Igor; Kaunitz, Jonathan D.

doi:10.1152/ajpgi.2000.279.2.g437

Cited by 56 publications

(40 citation statements)

References 45 publications

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“…Concentrations of protein and neutral and acidic sugars were measured by previously described methods (14,34,35). The mucus concentration was also measured by blotting the mucus on polyvinylidene difluoride membranes and staining it with periodic acid-Schiff reagent (PAS) or pH 2.5 Alcian blue (AB) (1).…”

Section: Methodsmentioning

confidence: 99%

Intestinal Adherence of Vibrio cholerae Involves a Coordinated Interaction between Colonization Factor GbpA and Mucin

et al. 2008

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The chitin-binding protein GbpA of Vibrio cholerae has been recently described as a common adherence factor for chitin and intestinal surface. Using an isogenic in-frame gbpA deletion mutant, we first show that V. cholerae O1 El Tor interacts with mouse intestinal mucus quickly, using GbpA in a specific manner. The gbpA mutant strain showed a significant decrease in intestinal adherence, leading to less colonization and fluid accumulation in a mouse in vivo model. Purified recombinant GbpA (rGbpA) specifically bound to N-acetyl-D-glucosamine residues of intestinal mucin in a dose-dependent, saturable manner with a dissociation constant of 11.2 M. Histopathology results from infected mouse intestine indicated that GbpA binding resulted in a time-dependent increase in mucus secretion. We found that rGbpA increased the production of intestinal secretory mucins (MUC2, MUC3, and MUC5AC) in HT-29 cells through upregulation of corresponding genes. The upregulation of MUC2 and MUC5AC genes was dependent on NF-B nuclear translocation. Interestingly, mucin could also increase GbpA expression in V. cholerae in a dose-dependent manner. Thus, we propose that there is a coordinated interaction between GbpA and mucin to upregulate each other in a cooperative manner, leading to increased levels of expression of both of these interactive factors and ultimately allowing successful intestinal colonization and pathogenesis by V. cholerae.Vibrio cholerae is the causative agent of the potentially lethal disease cholera. V. cholerae strains belonging to serogroups O1 and O139 are mainly responsible for cholera epidemics, while strains of other serogroups may cause sporadic outbreaks of the disease. Although the O139 strain has evolved recently, V. cholerae O1 biotype El Tor strains have still been responsible for most of the epidemics in recent years (20,26). In order to cause the disease, V. cholerae must adhere to the intestinal mucus barrier (52). The ability of V. cholerae to adhere to animal cells has been studied before (26,42), and various adherence factors have been proposed, including the virulence-associated toxin-coregulated pilus (5), outer membrane proteins (26, 42), and lipopolysaccharide (LPS) (11). Attachment of V. cholerae to abiotic surfaces has also been recently described (50). However, there is still no information about the factor(s) responsible for initial adherence of the bacteria to the intestine and whether the host plays any role in aiding the colonization of the intestine by the bacteria.Vibrios are marine organisms that adhere to chitin in the environment (12, 33) and utilize chitin as the sole source of nitrogen and carbon by using a family of glycosyl hydrolases, called chitinases (21). Genome analysis of V. cholerae O1 El Tor has revealed the presence of seven such chitinase genes (7), some of which have been characterized (27,37). One of these genes is the putative chitinase gene with locus number VCA0811, the product of which has been recently identified as a common adhesion molecule for both chitinou...

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Section: Methodsmentioning

confidence: 99%

Intestinal Adherence of Vibrio cholerae Involves a Coordinated Interaction between Colonization Factor GbpA and Mucin

et al. 2008

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“…The solutions bathing the serosal surface (external) were also defined and changed as needed. The collected perfusates were assayed for mucus content by WGA-lectin binding or by PAS staining of the filtrand retained on imobilon-P film (an adaptation of the dot blot technique) (2,18,35).…”

Section: Is There Evidence That Hco 3 ϫ Is Linked To Mucoviscidosis?mentioning

confidence: 99%

Role of epithelial HCO₃⁻ transport in mucin secretion: lessons from cystic fibrosis

Quinton

2010

American Journal of Physiology-Cell Physiology

167

149

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The invitation to present the 2010 Hans Ussing lecture for the Epithelial Transport Group of the American Physiological Society offered me a unique, special, and very surprising opportunity to join in saluting a man whom I met only once, but whose work was the basis, not only for my career, but also for finding the molecular defect in the inherited disease cystic fibrosis (CF). In this context, I will venture to make the tribute with a new explanation of why a mutation in a single gene that codes for an anion channel can cause devastation of multiple epithelial systems with pathogenic mucus. In so doing, I hope to raise awareness of a new role for that peculiar anion around which so much physiology revolves, HCO3−. I begin by introducing CF pathology as I question the name of the disease as well as the prevalent view of the basis of its pathology by considering: 1) mucus, 2) salt, and 3) HCO3−. I then present recent data showing that HCO3− is required for normal mucus discharge, and I will close with conjecture as to how HCO3− may support mucus discharge and why the failure to transport this electrolyte is pathogenic in CF.

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“…To elucidate the mechanism of lesion formation by selective COX inhibitors, we examined the effect of COX inhibitors on the distribution of mucus, an important factor in the protection of duodenal mucosa (Akiba et al, 2000(Akiba et al, , 2001. We found that the number of PAS-positive goblet cells in the villi Role of COX in the Protection of Duodenal Mucosa was significantly decreased by SC-560 and IND, but not by celecoxib, suggesting that production of mucus in goblet cells depends on PGs produced by COX-1 but not by COX-2.…”

Section: Drugmentioning

confidence: 99%

Cyclooxygenase (COX)-1 and COX-2 Both Play an Important Role in the Protection of the Duodenal Mucosa in Cats

Satoh

Amagase

Ebara

et al. 2012

J Pharmacol Exp Ther

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Although nonsteroidal anti-inflammatory drugs often cause ulcers in the duodenum in humans, the role of cyclooxygenase (COX) isoforms in the pathogenesis of duodenal ulcers has not been fully elucidated. We examined in cats the 1) ulcerogenic effects of selective COX-1 (SC-560, ketorolac) and COX-2 (celecoxib, meloxicam) inhibitors on the gastrointestinal mucosa, 2) effect of feeding and cimetidine on the expression of COX isoforms and prostaglandin E 2 (PGE 2 ) level in the duodenum, and 3) localization of COX isoforms in the duodenum. COX inhibitors were administered after the morning meal in cats once daily for 3 days. Gastrointestinal lesions were examined on day 4. Localization and expression of COX isoforms (by immunohistochemistry, Western blot) and PGE 2 level (by enzyme immunoassay) were examined. Results were as follows. First, selective COX-1 or COX-2 inhibitors alone produced marked ulcers in the duodenum but did not cause obvious lesions in the small intestine. Coadministration of SC-560 and celecoxib produced marked lesions in the small intestine. Second, feeding increased both the expression of COX isoforms and PGE 2 level in the duodenum, and the effects were markedly inhibited by pretreatment with cimetidine. Third, COX-1 was localized in goblet and Brunner's gland cells, Meissner's and Auerbach's plexus, smooth muscle cells, and arterioles; and COX-2 was observed in capillaries, venules, and basal granulated cells. The expression of COX isoforms in the duodenum is up-regulated by feeding, and inhibition of either COX-1 or COX-2 causes ulcers in the duodenum, suggesting that both isoforms play an important role in the protection of the duodenal mucosa.

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Dynamic regulation of mucus gel thickness in rat duodenum

Cited by 56 publications

References 45 publications

Intestinal Adherence of Vibrio cholerae Involves a Coordinated Interaction between Colonization Factor GbpA and Mucin

Intestinal Adherence of Vibrio cholerae Involves a Coordinated Interaction between Colonization Factor GbpA and Mucin

Role of epithelial HCO₃⁻ transport in mucin secretion: lessons from cystic fibrosis

Cyclooxygenase (COX)-1 and COX-2 Both Play an Important Role in the Protection of the Duodenal Mucosa in Cats

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Dynamic regulation of mucus gel thickness in rat duodenum

Cited by 56 publications

References 45 publications

Intestinal Adherence of Vibrio cholerae Involves a Coordinated Interaction between Colonization Factor GbpA and Mucin

Intestinal Adherence of Vibrio cholerae Involves a Coordinated Interaction between Colonization Factor GbpA and Mucin

Role of epithelial HCO3− transport in mucin secretion: lessons from cystic fibrosis

Cyclooxygenase (COX)-1 and COX-2 Both Play an Important Role in the Protection of the Duodenal Mucosa in Cats

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Role of epithelial HCO₃⁻ transport in mucin secretion: lessons from cystic fibrosis