Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis

Renes, Ingrid B.; Boshuizen, Jos A.; Nispen, Daniëlle J. P. M. Van; Bulsing, Nathalie P.; Büller, Hans A.; Dekker, Jan; Einerhand, Alexandra W. C.

doi:10.1152/ajpgi.00229.2001

Cited by 53 publications

(45 citation statements)

References 24 publications

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“…Although Muc-2 was not expressed in the stomach of healthy mice, we did observe expression of Muc-2 in the stomach after administration of indomethacin and at the ulcer margin of acetic acid-induced gastric ulcers. This observation is consistent with the elevated expression of Muc-2 in the intestine in experimental colitis 31 and in response to indomethacin administration. 32 An unexpected finding in this study was the sex difference in mucosal healing.…”

Section: Discussionsupporting

confidence: 89%

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Wallace

Vong

Dharmani

et al. 2011

The American Journal of Pathology

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Mucus is known to contribute significantly to the prevention and repair of mucosal damage throughout the gastrointestinal tract. Although not normally expressed in the stomach, mucin-2 (MUC-2, encoded by the MUC2 gene) is expressed in certain disease states. The aim of this study was to determine in a mouse model whether the absence of Muc-2 would result in impaired susceptibility to and healing of gastric mucosal injury. Acute gastric damage was induced in mice deficient in Muc-2 and in wild-type controls, through oral administration of indomethacin. Chronic gastric ulcers were induced by serosal application of acetic acid. The extent of injury and the extent of healing of the damage over time were examined in both models. Indomethacin administration caused similar levels of gastric damage in Muc-2-deficient and wild-type mice, but the erosions healed more slowly in the former. Acetic acid-induced gastric ulcers were initially similar in size in Muc-2-deficient and wildtype mice of both sexes, but ulcer healing was significantly impaired in male Muc-2-deficient mice. Induction of cyclooxygenase-2 in the stomach, in response to indomethacin-or acetic acid-induced ulceration, was significantly reduced in male Muc-2-deficient mice. This phenomenon, and the sex specificity, was also apparent in bone marrow-derived macrophages stimulated with endotoxin. These results demonstrate a marked impairment of gastric mucosal repair in male Muc-2-deficient mice that may be related to an insufficient induction of cyclooxygenase-2, an enzyme known to contribute to mucosal repair.

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Section: Discussionsupporting

confidence: 89%

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Wallace

Vong

Dharmani

et al. 2011

The American Journal of Pathology

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“…Proteins were isolated from frozen segments by homogenization of the tissue in 500 l of (Tris-) homogenization buffer containing Triton X-100 (BDH, Poole, England), 1% sodium dodecyl sulfate, and various protease inhibitors as previously described (48). Protein concentration was measured using a bicinchoninic acid protein assay reagent kit (Pierce).…”

Section: Methodsmentioning

confidence: 99%

Changes in Small Intestinal Homeostasis, Morphology,and Gene Expression during Rotavirus Infection of InfantMice

Boshuizen

Reimerink

Male

et al. 2003

J Virol

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134

123

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Rotavirus is the most important cause of infantile gastroenteritis. Since in vivo mucosal responses to a rotavirus infection thus far have not been extensively studied, we related viral replication in the murine small intestine to alterations in mucosal structure, epithelial cell homeostasis, cellular kinetics, and differentiation. Seven-day-old suckling BALB/c mice were inoculated with 2 ؋ 10 4 focus-forming units of murine rotavirus and were compared to mock-infected controls. Diarrheal illness and viral shedding were recorded, and small intestinal tissue was evaluated for rotavirus (NSP4 and structural proteins)-and enterocyte-specific (lactase, SGLT1, and L-FABP) mRNA and protein expression. Morphology, apoptosis, proliferation, and migration were evaluated (immuno)histochemically. Diarrhea was observed from days 1 to 5 postinfection, and viral shedding was observed from days 1 to 10. Two peaks of rotavirus replication were observed at 1 and 4 days postinfection. Histological changes were characterized by the accumulation of vacuolated enterocytes. Strikingly, the number of vacuolated cells exceeded the number of cells in which viral replication was detectable. Apoptosis and proliferation were increased from days 1 to 7, resulting in villous atrophy. Epithelial cell turnover was significantly higher (<4 days) than that observed in controls (7 days). Since epithelial renewal occurred within 4 days, the second peak of viral replication was most likely caused by infection of newly synthesized cells. Expression of enterocyte-specific genes was downregulated in infected cells at mRNA and protein levels starting as early as 6 h after infection. In conclusion, we show for the first time that rotavirus infection induces apoptosis in vivo, an increase in epithelial cell turnover, and a shutoff of gene expression in enterocytes showing viral replication. The shutoff of enterocyte-specific gene expression, together with the loss of mature enterocytes through apoptosis and the replacement of these cells by less differentiated dividing cells, likely leads to a defective absorptive function of the intestinal epithelium, which contributes to rotavirus pathogenesis.Rotaviruses are one of the most significant causes of gastroenteritis, malnutrition, and diarrhea in young children and animals (17, 28). Mortality rates are low in developed countries, where illness is usually self-limiting (64). However, each year more than 600,000 young children die in developing countries throughout the world (26). Rotavirus infection in children is mainly restricted to the small intestinal villus epithelium, resulting in the occurrence of total villus atrophy (3). Although rotavirus can infect older children and adults, diarrheal disease is primarily observed in children under 2 years of age (16,17,28).Rotavirus-induced diarrhea is thought to be caused by a combination of factors (55), which include a reduction in epithelial surface area, replacement of mature enterocytes by immature (crypt-like) cells (43), an osmotic effect resulting from ...

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“…Deparaffinized and rehydrated tissue sections from neonatal control mice and mice infected with the murine EDIM strain (10) were incubated overnight at 4°C with the following rabbit polyclonal antibodies: anti-NSP4(114-135) (directed against aa 114 to 135; 1:1,000 dilution), anti-NSP4(120-147) (directed against aa 120 to 147; 1:1,000 dilution), anti-SA11 (1:1,500 dilution), or anti-laminin-␤3 (1:500 dilution). Immunohistochemistry was carried out as described previously (10,69); however, antigen unmasking for laminin-␤3 was carried out by heating the sections for 10 min in 0.01 M sodium citrate (pH 6.0) at 100°C and by additional treatment with protease XXIV (Sigma) for 10 min at 37°C. The slides were analyzed by microscopy with a Nikon Eclipse 800 microscope and Leica IM-500 software.…”

Section: Methodsmentioning

confidence: 99%

Rotavirus Enterotoxin NSP4 Binds to the Extracellular Matrix Proteins Laminin-β3 and Fibronectin

Boshuizen

Rossen

Sitaram

et al. 2004

J Virol

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Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis

Abstract: . Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis.

Cited by 53 publications

References 24 publications

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Changes in Small Intestinal Homeostasis, Morphology,and Gene Expression during Rotavirus Infection of InfantMice

Rotavirus Enterotoxin NSP4 Binds to the Extracellular Matrix Proteins Laminin-β3 and Fibronectin

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