Distinct epithelial responses in experimental colitis: implications for ion uptake and mucosal protection

Abstract

In the present study, we aimed to investigate enterocyte- and goblet cell-specific functions during the different phases of acute colitis induced with dextran sulfate sodium (DSS). Rats were treated with DSS for 7 days, followed by a 7-day recovery period. Colonic tissue was excised on days 2 (onset of disease), 7 (active disease), and 14 (regenerative phase). Enterocyte functions were studied by the expression of carbonic anhydrases (CAs), sodium/hydrogen exchangers (NHEs) and intestinal fatty acid-binding protein (iFABP) and by alkaline phosphatase (AP) activity. The expression and secretion of the mucin Muc2 and trefoil factor family peptide-3 (TFF3) were used as parameters for goblet cell function. DSS induced a downregulation of the CAs, NHEs, and iFABP in some normal-appearing surface enterocytes and in most of the flattened-surface enterocytes during disease onset and active disease. During the regenerative phase most enterocytes expressed these genes again. Quantitative analysis revealed a significant decrease in CAs, NHEs, and iFABP expression levels during onset and active disease. During the regenerative phase, the expression levels of the CAs were restored, whereas the expression levels of the NHEs and iFABP remained decreased. In contrast, enterocyte-specific AP activity was maintained in normal and flattened enterocytes during DSS-induced colitis. Goblet cells continued to express MUC2 and TFF3 during and after DSS treatment. Moreover, Muc2 and TFF3 expression and secretion levels were maintained or even increased during each of the DSS-induced disease phases. In conclusion, DSS-induced colitis was associated with decreased expression of CAs, NHEs, and iFABP. The loss of these genes possibly accounts for some of the pathology seen in colitis. The maintenance or upregulation of Muc2 and TFF3 synthesis and secretion levels implies that goblet cells at least maintain their epithelial defense and repair capacity during acute inflammation induced by DSS.

Combined defects in epithelial and immunoregulatory factors exacerbate the pathogenesis of inflammation: mucin 2-interleukin 10-deficient mice

“…25 In addition, loss of differentiation of intestinal cells during damage, in general, has been shown in several animal models, by downregulation of distinct enterocyte-specific proteins. 14,35,36 The ABpositive cells at the crypt bases in the distal colon in the Muc2/IL-10 DKO mice could indicate transient expression of other mucins known to be expressed in the intestine or de novo expression of Muc6 mRNA as described for the Muc2 À/À mice. 14 Recent studies have implicated a role for membranebound mucins in signaling, contributing to the modulation of intestinal-cell proliferation and differentiation as reviewed by 37 Hollingsworth and Swanson.…”

Tissue-nonspecific alkaline phosphatase is activated in enterocytes by oxidative stress via changes in glycosylation

“…Both infiltrating leukocytes and intestinal epithelial cells appear to contribute to this phenomenon in vivo. 38,50 However, the increase due to infiltration of leukocytes is thought to be simply the result of cell accumulation, without intracellular changes in AP expression. Conversely, primary enterocytes show evidence of a change in isoform.…”

Mouse Model of Enteropathogenic Escherichia coli Infection

“…Increased numbers of goblet cells have been shown in other instances of injury (7,10,61,65), leading some to propose that this adaptive response allows goblet cell-secreted mucin to form a viscous gel that traps microorganisms and irritants and limits their access to the epithelium (4). In chemically induced intestinal inflammation, the expression and secretion of mucin increased with disease progression and differed in the proximal colon and the distal colon (48). Also, in the same model of inflammation, a loss of crypts and surface epithelium and the subsequent loss of goblet cells in some areas (47) were partly compensated for by increases in the numbers of goblet cells in elongated crypts and surface epithelium in other areas (48).…”

“…In chemically induced intestinal inflammation, the expression and secretion of mucin increased with disease progression and differed in the proximal colon and the distal colon (48). Also, in the same model of inflammation, a loss of crypts and surface epithelium and the subsequent loss of goblet cells in some areas (47) were partly compensated for by increases in the numbers of goblet cells in elongated crypts and surface epithelium in other areas (48). Furthermore, it has been reported that the overproduction and secretion of mucins are associated with inflammation caused by bacterial infection (59).…”