Biosynthesis and secretion of human colonic mucin glycoproteins.

Smith, A. C.; Podolsky, Daniel K.

doi:10.1172/jci113073

Cited by 32 publications

(10 citation statements)

References 28 publications

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“…These findings are similar to those previously reported in ulcerative colitis using incorporation of radiolabelled glucosamine rather than N-acetylglucosamine. These studies showed reduced [4] or normal [22] incorporation in inactive ulcerative colitis but increased incorporation in active ulcerative colitis [5], Glucosamine incorporation by Crohn's disease explants has however previously been reported to be normal [4].…”

Section: Discussionmentioning

confidence: 91%

Abnormal Mucosal Glycoprotein Synthesis in Inflammatory Bowel Is Not Related to Cigarette Smoking

et al. 1995

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Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn’s disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn’s disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 ± (SD) 7.1 dpm/μg biopsy protein, incorporation was increased in patients with active Crohn’s disease (mean 41.2 ± (SD) 10.4 dpm/μg biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 ± 7.8 dpm/μg biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 ± 13.8 dpm/μg biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n =58, mean 31.0 ± (SD) 7.52 dpm/μg biopsy protein; smokers, n = 27, mean 31.8 ± (SD) 6.1 dpm/μg biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn’s disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.

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Section: Discussionmentioning

confidence: 91%

Abnormal Mucosal Glycoprotein Synthesis in Inflammatory Bowel Is Not Related to Cigarette Smoking

et al. 1995

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“…Smith and Podolsky 14 reported that incorporation of radiolabeled precursors into mucin glycoproteins was somewhat increased in ulcerative colitis explant tissue of the sigmoid colon, whereas, according to Tytgat, 7 MUC2 precursor synthesis was significantly decreased in a group with active ulcerative colitis, compared with findings in the group with ulcerative colitis in remission, as well as in normal controls. Our previous study revealed that DSS induced goblet cell depletion in the distal side of the colon, resulting in the contraction of colon length after 7 days of treatment with DSS.…”

Section: Discussionmentioning

confidence: 97%

Compensatory response of colon tissue to dextran sulfate sodium-induced colitis

Nakano

Ohara

Kubota

et al. 1999

Journal of Gastroenterology

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Depletion of goblet cells (the main mucin-producing cells in the colon) is one of the most reliable histological characteristics of ulcerative colitis, whereas a major symptom of this disease is bloody diarrhea containing a large amount of mucus. The discrepancy between these phenomena was investigated in a time-course study in rats with experimental colitis induced by treatment with oral dextran sulfate sodium (DSS) for 1, 3, or 5 days. Biochemical analysis showed a reduction in mucin content in the distal side of the colon that was proportional to the duration of DSS administration. In the proximal side of the colon, however, there was a significant increase in mucin content already on the first day of treatment with DSS. This increase in colonic mucin content continued for the 5 days of treatment. In the distal side, both sulfomucin and sialomucin decreased proportionally to the duration of DSS administration. In the proximal side, there was an increase in high iron diamine-Alcian blue-positive mucins, and confirming the proliferation of goblet cells. The proliferated glands were predominantly sialylated. Goblet cell depletion and an increase in mucin production occurred in different parts of the colon. This phenomenon may be a type of compensatory function of colon tissue in response to the localized decrease of mucin production in certain portions of the colon.

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“…The diagnosis of coeliac disease was based on the presence of serum antibodies to endomysium, histological changes in small intestinal biopsy and other criteria as previously described [30]. Distal duodenal biopsies were fixed in 0·9% NaCl containing 10% formalin and paraffin embedded serial sections were used for morphological studies [29,31] and immunohistochemistry using rabbit anti‐human ITF antibody [15], polyclonal antibody to human colonic mucin [32,33], or pre‐immune serum. Xylene‐dewaxed and alcohol rehydrated paraffin sections were heated in a microwave with 0·01 m trisodium citrate solution.…”

Section: Methodsmentioning

confidence: 99%

Selective reduction of intestinal trefoil factor in untreated coeliac disease

Ciacci¹,

Vizio

Seth

et al. 2002

Clinical and Experimental Immunology

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SUMMARYThe trefoil factor family (TFF) encompasses small peptides of which intestinal trefoil factor (ITF) is expressed specifically in goblet cells of the small and large intestine. Previous studies have shown that ITF plays an important role in mucosal protection and repair. Coeliac disease represents a model of immune-mediated small intestinal inflammation and damage, with recovery on gluten-free diet. The aim of this study was to investigate the expression of ITF in the distal duodenal mucosa of subjects with coeliac disease, before and after treatment with a gluten-free diet. Expression of ITF and mucin in the distal duodenal biopsies from treated ( n = 11) and untreated ( n = 9) coeliac subjects and controls ( n = 8) was investigated by immunohistochemistry and semiquantitative PCR. In untreated coeliac disease, there was reduction of ITF immunoreactivity in goblet cells but mucin expression was preserved. Mucosal recovery on gluten-free diet was associated with increased ITF immunoreactivity in goblet cells. There was also reduction in the expression of ITF transcripts, relative to MUC2 mRNA, in untreated coeliac duodenal samples, with recovery on gluten-free diet. Our study suggests that there is a selective reduction in the expression of the ITF gene in untreated coeliac disease. Recovery of ITF expression on a gluten-free diet suggests that the mucosal immune system regulates goblet cell differentiation and ITF expression in the human intestinal mucosa.

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Biosynthesis and secretion of human colonic mucin glycoproteins.

Cited by 32 publications

References 28 publications

Abnormal Mucosal Glycoprotein Synthesis in Inflammatory Bowel Is Not Related to Cigarette Smoking

Abnormal Mucosal Glycoprotein Synthesis in Inflammatory Bowel Is Not Related to Cigarette Smoking

Compensatory response of colon tissue to dextran sulfate sodium-induced colitis

Selective reduction of intestinal trefoil factor in untreated coeliac disease

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