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At least 19 recordsLinked to original sources

PubMed1976

Human intestinal goblet cell mucin.

Goblet cell mucin (GCM) has been purified for the first time from mucosal scrapings of human small intestine. Proteolytic enzymes and organic solvents were avoided during the isolation procedure. The mucin was purified by Sepharose 4B and 2B column chromatography of high-speed supernatant fractions. The most purified fraction was compared with rat intestinal GCM. The two were similar with respect to chemical composition, antigenic features, and polyacrylamide disc gel electrophoresis. The major chemical differences included a higher hexosamine-fucose and hexosamine-sialic acid ratio in human mucin. The two mucins showed strong concentration dependence in sedimentation velocity studies. Human mucin at a concentration of 0.2 to 1.5 mg protein per millilitre gave multiple associated peaks with variable So values (10.8-36.6). Rat mucin, in contrast, gave a constant (although polydisperse) pattern with So = 15.15. To explore these differences both mucins were stained with periodic acid - Schiff reagent and subjected to band ultracentrifugation at concentrations of 0.6-1.9 mug protein per millilitre. At this low concentration, rat mucin did not change in its sedimentation characteristics. In contrast, human GCM produced a single peak with So = 37.9. Thus dilution abolished polydispersity in the human but not the rat mucin, suggesting that intermolecular bonding forces in the human mucin are weaker.

Amino Acids↗

PubMed2026

Colitogenic Environment Suppresses Notch/Mechanistic Target of Rapamycin-Mediated Epithelial Proliferation to Promote Goblet Cell Differentiation in the Colon.

Epithelial barrier dysfunction is a hallmark of inflammatory bowel diseases; however, the mechanisms underlying such impairment remain incompletely understood. In the present study, a dextran sulfate sodium-induced colitis model was used to investigate how the inflammatory environment damages the intestinal mucosa. The results demonstrated that colitogenic ambiance enhances intestinal epithelial cell death, delays epithelial cell proliferation, and exacerbates mucosal erosion. Unexpectedly, this work identified a previously unrecognized role for Notch signaling in mediating these effects. Specifically, the colitogenic milieu reduces Notch/mechanistic target of rapamycin complex 1 (mTORC1)-mediated intestinal epithelial cell proliferation to promote goblet cell differentiation. Chemical activation of Notch signaling stimulated intestinal epithelial cell proliferation and reduced goblet cell differentiation in the colitic mucosa, further aggravating mucosal damage. Conversely, inhibition of Notch or mTORC1 signaling during mucosal repair reduced intestinal epithelial cell proliferation and enhanced goblet cell differentiation, corroborating the implication of Notch and mTORC1 signaling in both processes. Collectively, these findings uncover a context-dependent role for the Notch-mechanistic target of rapamycin axis in regulating intestinal epithelial cell proliferation and differentiation in the colitic mucosa and suggest that its targeted modulation may hold therapeutic potential in inflammatory bowel diseases.

Animals↗

PubMed1975

Stimulation of proteolytic digestion by intestinal goblet cell mucus.

Intestinal goblet cell mucus (GCM) was added to incubations of casein and trypsin (or chymotrypsin) to discover whether mucus could inhibit proteolysis. Contrary to expectation, GCM stimulated casein hydrolysis, reaching a maximum effect at a GCM to casein ratio (w/w) of 0.083. GCM did not contain proteolytic enzymes or proenzymes as contaminants, nor did GCM serve as a substrate for trypsin. Stimulation was not reduced by removing 85% of the sialic acid from GCM. Harsh physical treatment (boiling and freezing) of casein decreased (50%) the GCM effect, as did partial predigestion of casein by trypsin, and elevation of trypsin concentration beyond 3 mug per ml. Thus the undegraded structure of casein appeared to be important for the stimulation of proteolysis by GCM. GCM also enhanced the hydrolysis by trypsin of intestinal brush border membrane protein, but had no effect on the hydrolysis of hemoglobin, albumin, or benzoyl arginine ethyl ester. These results suggest that GCM reacts with specific substrates, in a fashion which promotes their digestion by trypsin or chymotrypsin.

Albumins↗

PubMed2026

Single-cell transcriptomics reveals that air-liquid interface culture promotes goblet cell differentiation and inhibits glycolysis in organoid cell monolayers.

Faithfully recapitulating the cellular heterogeneity of the intestinal epithelium is essential when using organoid models. Air-liquid interface (ALI) culture has been shown to promote secretory cell differentiation, but its impact on gene expression in each epithelial cell type remains unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize the cellular heterogeneity of rabbit cecum-derived organoid monolayers grown under immerged or ALI conditions. We then compared these organoid cell type-specific gene expression profiles to a scRNA-seq atlas of the rabbit cecal epithelium in vivo. We selected the rabbit model notably because, unlike mice, it possesses BEST4+ epithelial cells, a newly discovered subset of mature absorptive cells. Our analysis revealed a high degree of transcriptomic similarity between in vivo and organoid-derived stem and transit-amplifying cells. ALI culture markedly enhanced the differentiation of the secretory lineage, especially goblet cells, whose transcriptome closely resembled that of in vivo goblet cells. Furthermore, ALI was the only condition allowing the detection of enteroendocrine cells. BEST4+ cells, however, were absent from organoids in immerged or ALI conditions despite their presence in vivo. In addition, ALI culture led to a consistent downregulation of hypoxia and glycolysis-associated genes across all cell types, which suggests a metabolic shift likely driven by increased oxygen availability in ALI conditions. Cell-cell communication analyses further indicated that ALI more closely mirrored in vivo patterns than immerged condition. Altogether, these results demonstrate that ALI culture allows for better recapitulation of the in vivo cellular heterogeneity and molecular signatures of the intestinal epithelium.NEW & NOTEWORTHY Using single-cell RNA sequencing, this study shows that air-liquid interface (ALI) culture enhances secretory lineage differentiation of intestinal organoid cell monolayers and improves transcriptomic similarity to the native epithelium. ALI reduced hypoxia-associated gene expression and better recapitulates in vivo-like cell-cell interactions, supporting its value for modeling intestinal epithelial heterogeneity in organoids.

Animals↗

PubMed1979

[Histological studies of goblet cell counts in human conjunctiva (author's transl)].

In 121 healthy subjects of all age groups the goblet cells were counted by means of conjunctival biopsies; none of these individuals showed any inflammatory or degenerative changes in their eye lids, conjunctivae or corneas. Three groups were distinguished: a small group with relatively few, a large group with an average number and a third small groups with a relatively large number of goblet cells. The number of goblet cells was usually between 26 and 40 to the square mm, but fluctuated to a great extent in all three groups. On determining age distribution, the average goblet cell counts were found to be astonishingly similar: they did not vary significantly in the different age groups. At most, one could say the goblet cell count is slightly lower from age 61 onward.

Adolescent↗

PubMed1978

The effect of isoprenaline and pilocarpine on mitotic index and goblet cell number in rat respiratory epithelium.

The effect of both isoprenaline (IPN) and pilocarpine (PCP) on mitotic activity and goblet cell number has been studied at 5 levels of the bronchial tree in male and female animals. While both drugs increased mitotic index and goblet cell number at most of the airway levels studied, differences in their effect were detected. After both drugs, nuclei in division were more often superficial within the epithelium than basal but IPN caused a greater increase in mitotic index than PCP. IPN increased goblet cell number at all levels, PCP only in the trachea and larger intrapulmonary airways. The types of goblet cell increased by IPN were particularly those containing acid glycoprotein, whereas PCP increased all types of goblet cell, that is, both those containing neutral and acid glycoprotein. After the drugs, the concentration of cells per unit length of airway epithelium was higher than normal. This is the first study demonstrating the effect of these two drugs on both goblet cell number and cell division. While the two drugs differ in their pharmacological action, the result of their stimulation of airway epithelium is similar. The way in which each effect is produced is discussed.

Animals↗

PubMed1978

Acid mucins in human intestinal goblet cells.

Acid mucins in goblet cells of the duodenum, jejunum and ileum of neonates and infants with cystic fibrosis (CF) and without CF were measured by scanning microdensitometry after alcian blue staining according to the protocol of McCarthy and Reid (1963) which characterises four groups of acidic mucins. In CF infants over 6 mth of age, but not in controls, there was an increase along the gut from duodenum to ileum of both weakly acidic and strongly acidic sulphomucins. In the ileum the increase was in total mucins from 6 mth previously in the same CF patients and this difference could be accounted for by an increase of sialidase-resistant mucins. The increase in sulphomucins was more marked at the tip than at the base of the villi. In CF neonates there was significant difference in the quantities of acidic mucins. The question whether the mucins of CF are chemically abnormal or merely accumulated to an abnormal extent is probably best investigated by analysis of sialidase-resistant mucins and sulphomucins of the ileum and strongly acidic sulphomucins of the duodenum and jejunum in CF infants over 6 mth of age.

Cell Count↗

PubMed1979

Immune regulation of intestinal goblet cell differentiation. Specific induction of nonspecific protection against helminths?

Goblet cell differentiation (GCD) was studied in the intestines of rats infected with Nippostrongylus brasiliensis since an important component of the immune expulsion of this parasite is thought to be nonspecific. An increase in the proportion of villous goblet cells occured at the time of worm expulsion during a primary infection. GCD was augmented by the passive transfer of immune thoracic duct lymphocytes and immune serum in infected rats but not in normal controls. Since drug-induced expulsion of the worms did not induce comparable changes, it was concluded that increased GCD in passively immunized rats was not simply a repair phenomenon. Passive protection with serum was abrogated by reserpine and prednisolone and GCD was depressed in the recipients of these drugs. The possibility that goblet cell differentiation and mucus release are part of the nonspecific component of worm expulsion is discussed.

Animals↗

PubMed1978

Ultrastructure of the goblet cell type of adenocarcinoid of the appendix.

Two examples of the goblet cell form of adenocarcinoid were studied with electron microscopy. Mucin was present in the form of large and small vacuoles or small patches of denser mucin granules. A small population of cells had a complement of organelles similar to the more obvious goblet cells but contained little or no identifiable product. Enterochromaffin cells were similar to those seen in normal midgut and in conventional carcinoids of midgut derivation. Enterochromaffin granules and mucin were not mixed with one another. Cell types transitional between mucinous and enterochromaffin were not found. Although study of plasmalemmae was hindered to a degree by artifacts due to tengential sectioning and, possibly, insufficiently rapid fixation, we favor the interpretation that the goblet cell type of adenocarcinoid is composed of two separate classes of cells.

Adenocarcinoma↗

PubMed1976

Distribution and density of goblet cells in the middle ear in children.

On dissected mucosa stained by the PAS-alcian blue whole-mount method the density and distribution of goblet cells in various parts of the middle ear was determined in 13 children, ranging in age from 9 days to 14 years. Goblet cells, of an irregular distribution, were found in all parts of the middle ear, but in varying density, decreasing in a given sequence from the hypotympanum anteriorly, posteriorly, promontory anteriorly and in the middle, niches of the oval and round windows, epitympanum, antrum, posterior part of the promontory, and mastoid process. During pathological actions, especially tubal occlusion, the goblet-cell density increases in all parts, simultaneously with epithelial metaplasia and new-formation of mucous glands. When the pathological stimulus ceases, the goblet-cell density again falls. In entirely normal infants and in children aged 2-4 years the goblet-cell density was found to be somewhat higher than in normal adults.

Adolescent↗

PubMed1977

Irreversible bronchial goblet cell metaplasia in hamsters with elastase-induced panacinar emphysema.

A single intratracheal instillation of pancreatic elastase in hamsters induces a lesion resembling human panacinar emphysema. This paper reports the occurrence of irreversible goblet cell metaplasia in the bronchial epithelium of hamsters similarly exposed to elastase. The goblet cell change was dose related; a dose of 0.1 mg/100 g body wt or less at 16 days, produced slight or moderate goblet cell metaplasia in fewer than half the animals, whereas 84% of animals treated with a dose between 0.2 and 0.5 mg/100 g body wt developed goblet cell metaplastic lesions, more than half of which were considered to be severe. The percentage of goblet cells in the epithelium of elastase-treated hamsters (32.5) was significantly higher (P less than 0.005) than that of unexposed (12.2) and saline-exposed controls (18.7). All hamsters examined 6 and 12 mo after elastase treatment showed the lesion. The pathogenesis of the changes is unclear but the possibility is raised that the bronchial changes may be due to disturbance of an endogenous protease-antiprotease system. The findings suggest the hypothesis that, under appropriate circumstances, a single pulmonary insult in man could lead to a permanent lung injury demonstrating the anatomic lesions of both chronic bronchitis and panacinar emphysema.

Animals↗

PubMed1978

MPG protection and goblet cell kinetics in mouse jejunum.

Experiments were undertaken to study the goblet cell changes in the jejunum of mice irradiated in the presence and absence of the protective drug 2-mercaptopropionylglycine (MPG). One group of adult Swiss albino mice of 6 to 8 weeks was injected with the drug (MPG) intraperitoneally and a second group was injected with distilled water in the same manner and served as a control. 15-30 minutes after injection animals from both the groups were exposed to a Co-60 source to give a total dose of 1000 R at the rate of 25 R/min. Three animals from each group were sacrificed at different successive intervals. 5 micron paraffin sections of the jejunum were prepared and goblet cells were counted in the crypt and villus region. The results from the two groups were compared. The results from MPG treated mice indicated that there was a protection from the radiation-induced changes. The drug accelerated the regeneration process leading to the restoration of normal number of goblet cells by the last interval studies.

Amino Acids, Sulfur↗

PubMed1975

Density of goblet cells in chronic secretory otitis media: findings in a biopsy material.

In 30 ears from 24 children with chronic secretory otitis the density of goblet cells and of glands was determined on biopsies from the anterior part of the promontory. The goblet-cell and gland density proved to be highly increased in all cases, with marked individual variations. The median density of goblet cells was 142 cells/field, corresponding to 8,000 cells/mm-2. This substantiates the fact that in chronic secretory otitis the mucous secretion is a product of goblet cells and mucous glands and confirms the secretory pathogenesis of the disease.

Adolescent↗

PubMed1979

Mucosubstance histochemistry of Brunner's glands, pyloric glands and duodenal goblet cells in the ferret.

The mucosubstance of Brunner's glands, pyloric glands and duodenal goblet cells were studied using the various histochemical methods. The secretions of both Brunner's and pyloric glands were similar in their histochemical reactions. They contained neutral mucosubstances as in these glands in man. The duodenal goblet cells showed variations in their histochemical characters. (i) The secretions of most of the deep cells and the majority of superficial cells contained sialidase-labile and sialidase-resistant sialomucins. (ii) There were a few superficial and occasional deep cells, the secretions of which contained sulphated mucosubstances. (iii) There were some goblet cells, more in the villi than in the crypts, the secretions of which contained a mixture of sialomucins and a sulphated mucin. The sialomucin was mostly sialidase-labile and partly sialidase-resistant.

Animals↗

PubMed1979

Purification of human intestinal goblet cell antigen (GOA), its immunohistological demonstration in the intestine and in mucus producing gastrointestinal adenocarcinomas.

Goblet cell antigen (GOA) was purified from gastric signet ring cell carcinoma. It was immunogenic and was used to produced antisera which stained goblet cells of the small and large intestine and of intestinalized gastric mucosa by indirect immunological methods. Various types of gastric and colonic cancer contained GOA. These findings demonstrate a histiogenic relationship between intestinal goblet cells, various gastrointestinal cancers and associated premalignant conditions.

Adenocarcinoma↗

PubMed1975

Calcium binding to intestinal goblet cell mucin.

1. Binding of Ca-2+ to goblet cell mucin of rat small intestine was studied using equilibrium dialysis against 0.01 M Tris/HCl buffer (pH 7.4) and tracer amounts of 45-CaCl2. Binding was found to reach saturation at a Ca free -2+ concentration of 0.1--1.0 mM, to be independent of temperature (4-37 degrees C), and to increase with increasing pH (5.0-8.7). At low concentrations of Ca free -2+ (smaller than 0.03 mM) the binding curve was sigmoidal, suggesting positive cooperativity of binding sites and a possible change in the tertiary structure of the mucin. Binding was markedly reduced, and sigmoidicity abolished, by removal of sialic acid from the mucin, or by adding 0.14 M NaCl to the dialysis medium. This latter finding suggests that, in vivo, other cations would compete for Ca-2+ binding ligands. 2. Under conditions mimicking those used for binding studies, CaCl2 (10- minus 5 M) was found to cause a small increase (0.03 units) in the absorbance of mucin solutions, especially in the ultraviolet region, possibly indicating increased light scattering. No change in the solubility of the mucin was observed after the addition of CaCl2 (10- minus 6-10- minus 4 M). A significant decrease in viscosity of the mucin was noted, however, with the addition of CaCl2 (10- minus 6-10- minus 2 M). Together with the binding data, these findings suggested that during binding, Ca-2+ combines with negative charges on goblet cell mucin (especially those of sialic acid carboxyl groups) and induces contraction or folding of the macromolecule which promotes cooperative cation binding. No evidence was obtained to suggest that CaCl2 caused precipitation, polymerization or gelation of the mucin in 0.01 M Tris/HCl.?

Animals↗

PubMed1979

Intestinal goblet cell mucus release. II. In vivo stimulation by antigen in the immunized rat.

We previously reported that the infusion of certain soluble immune complexes stimulated mucus release from the rat small intestine in vivo. The present studies sought to evaluate the response of the intestine of normal and immunized rats to the infusion of antigen alone. One hour after the intraduodenal infusion of antigen, small intestinal washings were obtained and analyzed for the presence of 35S-labeled, high m.w. glycoprotein of goblet cell origin. The amount of goblet cell glycoprotein released was estimated from the radioactivity present in the void volume of a Sepharose 4B gel filtration column. The release of goblet cell mucus was enhanced by antigen stimulation in orally immunized animals. The discharge of goblet cell mucus was not increased after antigen infusion in animals immunized by the i.p. route despite the induction of high levels of serum antibody. The inability to demonstrate release of mucus after antigen challenge in systemically immunized rats suggests that the amount or the type(s) of antibody required at the mucosal surface is produced only after oral immunization.

Animals↗

PubMed1976

Identification of glycoproteins in goblet cells of epidermis and gill of plaice (Pleuronectes platessa L.), flounder (Platichthys flesus (L.)) and rainbow trout (Salmo gairdneri Richardson).

A quantitative analysis has been made of the glycoproteins present in the goblet cells of the epidermis, gill filaments and gill lamellae of three species of teleost fish. The glycoproteins have been identified by a combination of techniques, including the use of the enzyme sialidase followed by Alcian Blue staining, at PH 2.6 or 1.0, in combination with periodic acid-Schiff. The selected fish were representative of species living in marine, freshwater and estuarine environments. The range of glycoproteins identified in these fish was similar to that found in mammalian tissue in that both neutral and acid glycoproteins were present, the latter included both sialomucins sensitive and resistant to sialidase, and sulphomucin. A single goblet cell contained either neutral or acid glycoproteins alone or in combination. Only the epidermis of the plaice and rainbow trout contained uniform cell populations producing acid glycoproteins, the former sulphomucin and the latter mainly sialomucin. At each site in the flounder and in the gill epithelia of the plaice and rainbow trout, the goblet cell population was mixed, with cells producing each type of glycoprotein. The number of goblet cells producing each type of glycoprotein varied at each tissue site.

Alcian Blue↗