Disease relevance of Goblet Cells

• Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma [1].
• Glycoconjugate composition of colorectal goblet cell mucin was characterized according to the anatomical distribution of lectin-binding sites in mucosal biopsies from 35 control subjects and 55 patients with inflammatory bowel disease [2].
• Within areas of intestinal metaplasia, a few goblet cells immunostained for pS2 and putative ulcer associated cell lineage was seen with a pattern of trefoil peptide localization similar to the ileum [3].
• RESULTS: C57BL/6(+/+), IFN-gamma(-/-), and IL-12(-/-) mice developed patterns of colitis characterized by distortion of crypts, loss of goblet cells, and mononuclear cell infiltration with fibrosis of the mucosal layer [4].
• Analysis of lung tissue from patients with a variety of pulmonary diseases revealed a strong inverse correlation between FOXA2 and goblet cell hyperplasia [5].

High impact information on Goblet Cells

• The increase in goblet cell number is further accelerated by 10(-9) molar thyroxine but is prevented by 10(-6) molar hydrocortisone [6].
• Gfi1(-/-) mice lack Paneth cells, have fewer goblet cells, and supernumerary enteroendocrine cells [7].
• An increase in the number of goblet cells occurs within 8 h of induction, due to an effect of Notch on post-mitotic cells, not on precursors [8].
• In vivo studies of CF mouse nasal epithelia revealed an increase in goblet cell number that was associated with decreased ASL volume rather than abnormal [Cl(-)] [9].
• In this issue of the JCI, Tyner et al. show, in a mouse model of chronic mucous hypersecretion, that ciliated epithelial cell apoptosis is inhibited by EGFR activation, allowing IL-13 to stimulate the differentiation of these cells into goblet cells, which secrete mucus [10].

Chemical compound and disease context of Goblet Cells

• The inhibitory effect of FTY720 on airway inflammation, induction of bronchial hyperresponsiveness, and goblet cell hyperplasia could be confirmed in an actively Ag-sensitized murine asthma model, clearly indicating that Th2 cell-driven allergic diseases such as asthma could benefit from such treatment [11].
• The presence of STn and cryptic Tn within normal colorectal goblet cells and the absence of Tn expression within colorectal cancer secretory mucin contradicts the generally accepted concept of cancer-specific incomplete glycoprotein synthesis within these neoplasms [12].
• BACKGROUND: An allergen challenge to the airways of sensitized mice causes eosinophilic airway inflammation and degranulation of goblet cells, which lead to airway obstruction [13].
• Treatment with dexamethasone inhibited eotaxin expression and completely abolished eosinophil accumulation, but it did not affect AHR, MUC5AC overexpression, or goblet cell hyperplasia induced by IL-13 [14].
• Moreover, goblet cell metaplasia and airway responsiveness to methacholine could be reduced significantly by the IL-4/IL-13 inhibitor [15].

Biological context of Goblet Cells

• These results demonstrate that the expression of lectin-binding sites in human large intestinal goblet mucin is specifically altered in inflammatory bowel disease, indicating that there are changes in glycosylation of colorectal mucin consistent with alterations in goblet cell differentiation [2].
• To assess the role of goblet cells in the intestine, we generated transgenic mice in which approximately 60% of goblet cells were ablated by the expression of an attenuated diphtheria toxin (DT) gene driven by the ITF promoter; other cell lineages were unaffected [16].
• In this study, we analyzed the mechanism of KGF modulation of goblet cell differentiation through characterization of its effects on ITF gene expression [17].
• METHODS: Subclone H2 of the human colonic epithelial cell line HT-29, which can be induced to intestinal goblet cells, was treated with KGF and characterized by Northern and Western blot analyses, transient transfection assays, and electrophoretic mobility shift assays (EMSAs) [17].
• It has been used here to show that beta-catenin is required for the maintenance of intestinal cell proliferation and is implicated in goblet cell differentiation and enterocyte-matrix attachment [18].

Anatomical context of Goblet Cells

• These data show that human colonic mucosa contains discrete subpopulations of goblet cells that produce distinctive combinations of specific mucin glycoprotein species [19].
• CFTR expression was detected at the luminal surface of reabsorptive sweat ducts and airway submucosal glands, at the apex of ciliated cells in pseudostratified respiratory epithelia and of isolated cells of the villi of duodenum and jejunum, and within intracellular compartments of intestinal goblet cells [20].
• RESULTS: In the normal small intestine and colon, an antibody recognizing the MUC2 apomucin stained goblet cells [21].
• Polyclonal antibodies raised against purified human colonic mucin, and also a monoclonal antibody against a protease-sensitive epitope of human colonic mucin, stained secretory granules of all differentiated goblet cells within N2 cell monolayers but did not stain predifferentiated goblet cells lacking large secretory granules [22].
• This was accompanied by morphological evidence of gland formation and mucin secretion and the appearance of discrete goblet cell and enterocyte populations [23].

Associations of Goblet Cells with chemical compounds

• We studied glycoprotein content of human colonic goblet cells, using a library of monoclonal antibodies (MAbs) directed against purified human colonic mucin (HCM) [19].
• Proteolytic activity was required for mucin release by P. aeruginosa elastase, but such release in goblet cells was not mediated by cyclic AMP [24].
• Grown in the absence of glucose, these cells formed homogeneous epithelial monolayers of columnar cells with typical goblet cell morphology [22].
• CONCLUSIONS: Guanylin is expressed in mature goblet cells [25].
• In contrast, both the brush-border and goblet cells were intensely fluorescent after exposure to Triticum vulgaris [26].

Gene context of Goblet Cells

• This chronic switch in epithelial behavior exhibits genetic susceptibility and depends on persistent activation of EGFR signaling to PI3K that prevents apoptosis of ciliated cells and on IL-13 signaling that promotes transdifferentiation of ciliated to goblet cells [27].
• Anti-MUC2 antibody was mainly reactive with intestinal goblet cells and cervical mucous cells [28].
• The human MUC2 gene maps to chromosome 11p15, where three additional mucin genes have been located, and encodes the most abundant gastrointestinal mucin normally expressed in the intestinal goblet cell lineage [29].
• MUC5AC is generally recognized to be a major airway mucin because MUC5AC is highly expressed in the goblet cells of human airway epithelium [30].
• Thus, STAT6 activation mediates a transcriptional enhancement of TFF3 by induction of de novo synthesized protein in goblet cells [31].

Analytical, diagnostic and therapeutic context of Goblet Cells

• Radioimmunoassay of human intestinal goblet cell mucin. Investigation of mucus from different organs and species [32].
• Consistent with this, in situ hybridization showed MUC2 messenger RNA (mRNA) only in goblet cells and MUC3 mRNA in both goblet and absorptive cells [21].
• The two lactose-binding lectins found in adult chicken intestine, chicken-lactose-lectin-1 (CLL-1) and chicken-lactose-lectin-11 (CLL-11), were localized within the vesicles of the mucin-secreting goblet cells by indirect immunofluorescence and immunoperoxidase staining methods [33].
• We conclude that the peptide NT is involved in colonic goblet cell release and mucosal mast cell activation after immobilization stress [34].
• Immunoelectron microscopy demonstrated the reactivity with mucin droplets in a homogeneous granular pattern inside the globules of goblet cells [35].

References