MUC Genes Are Differently Expressed During Onset and Maintenance of Inflammation in Dextran Sodium Sulfate-Treated Mice

Abstract

Colonic mucosal protection is provided by mucous gel, mainly composed of secreted (Muc2) and membrane-bound (Muc1, Muc3, Muc4) mucins. Our aim was to determine the expression profile of secreted and membrane-bound mucins in experimental dextran sulfate sodium (DSS)-induced colitis. Acute colitis was induced in Balb/C mice by oral administration of 1.0% DSS (5 days) and chronic colitis was maintained by subsequent 0.15% DSS treatment (28 days). Clinical symptoms (mortality, weight gain), stool scores, and MPO activity confirmed the inflammatory state in the two phases of colitis. Muc2 gene expression was not modified by colitis, whereas Muc3 gene expression was increased (x2) only in the cecum and the distal colon of mice after acute colitis. Muc1 and Muc4 mRNA levels were more significantly increased in the cecum (x8-10) than in colonic segments (x4) after acute colitis. TFF3 involved in mucosal repair was up-regulated during colitis induction. These results indicate that Muc and TFF3 genes are regulated early in inflammation and suggest that their mRNA levels could be used as early markers of inflammation.

Glucocorticoid Availability in Colonic Inflammation of Rat

“…Assuming that glucocorticoids decrease MPO activity [37] and the influx of inflammatory cells into the colon of TNBS rats [39], it is obvious that the changes in the local metabolism of corticosterone are not able to modulate granulocyte migration and activation. In contrast to our expectation, neither carbenoxolone nor budesonide suppressed MUC-2 expression even if colitis modulates MUC gene expression [40], and experiments performed with intestinal mucus-secreting cell lines showed modulation of transcript levels for various mucins by IL-1 and corticosteroids [41,42].…”

Early-stage blocking of Notch signaling inhibits the depletion of goblet cells in dextran sodium sulfate-induced colitis in mice

“…In human IBD and animal experimental colitis, disease progression is accompanied by the depletion of goblet cells and reduction in MUC2 expression [42][43][44]. MUC2-deficient mice are known to develop spontaneous colitis [45].…”

Avaliação do número de células caliciformes nas criptas da mucosa colônica com e sem trânsito intestinal

“…A single layer of cells juxtaposed with one another and attached to the basement membrane separating the interior of the intestinal lumen, with high bacterial concentration, from the sterile inner layers forming the intestinal wall 2 . This functional barrier is composed of multiple lines of defense, represented mainly by the layer of mucus covering the epithelial surface, the apical and basolateral membrane cell, the complex system of junctions and the basal membrane 1,[3][4][5] . The mucus covering the intestinal epithelium, secreted by goblet cells present in the glands of entire digestive tract, form the first line of defense of the colonic mucosa.The goblet cells vary in number over the different segments of the large intestine, increasing as it progresses towards the more caudal segments, where they occupy virtually the entire length of the glands.…”

“…Changes in goblet cell population, when comparing the different colon segments, are related to distinct physiological functions performed by each portion of the intestinal mucosa 6 . In the colon, the mucus layer, besides the lubricating function facilitating the progression of the fecal contents, provides protection against chemical attack caused by antigens, toxins and digestive enzymes existing within the intestinal lumen 3,4 . The mucus also possesses antibacterial properties, as it reduces the bacterial population in direct contact with the epithelial surface, hindering translocation to the internal environment 1,3,4,7 .…”

“…In the colon, the mucus layer, besides the lubricating function facilitating the progression of the fecal contents, provides protection against chemical attack caused by antigens, toxins and digestive enzymes existing within the intestinal lumen 3,4 . The mucus also possesses antibacterial properties, as it reduces the bacterial population in direct contact with the epithelial surface, hindering translocation to the internal environment 1,3,4,7 . Abnormalities in the secretion, composition and distribution pattern of mucins in the intestinal crypts have been demonstrated in several inflammatory diseases that affect the colon 6,8 .…”