2,964 results on '"MUCUS LAYERS"'
Search Results
2. The Inner of the Two Muc2 Mucin-Dependent Mucus Layers in Colon Is Devoid of Bacteria
- Author
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Johansson, Malin E. V., Phillipson, Mia, Petersson, Joel, Velcich, Anna, Holm, Lena, and Hansson, Gunnar C.
- Published
- 2008
- Full Text
- View/download PDF
3. Bacterial Populations and Adaptations in the Mucus Layers on Living Corals
- Author
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Ducklow, Hugh W. and Mitchell, Ralph
- Published
- 1979
4. Survey of Antibiotic-producing Bacteria Associated with the Epidermal Mucus Layers of Rays and Skates
- Author
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Kim B. Ritchie, Melbert Schwarz, Joseph Mueller, Valeri A. Lapacek, Daniel Merselis, Catherine J. Walsh, and Carl A. Luer
- Subjects
antibiotic producing bacteria ,antibacterial screening ,pathogens ,epidermal mucus ,stingray ,skate ,Microbiology ,QR1-502 - Abstract
Elasmobranchs represent a distinct group of cartilaginous fishes that harbor a remarkable ability to heal wounds rapidly and without infection. To date very little work has addressed this phenomenon although it is suggested that antibiotic capabilities associated with epidermal surfaces may be a factor. The study of benefits derived from mutualistic interactions between unicellular and multicellular organisms is a rapidly growing area of research. Here we survey and identify bacterial associates of three ray and one skate species in order to assess the potential for antibiotic production from elasmobranch associated bacteria as a novel source for new antibiotics.
- Published
- 2017
- Full Text
- View/download PDF
5. Composition and functional role of the mucus layers in the intestine
- Author
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Johansson, Malin E. V., Ambort, Daniel, Pelaseyed, Thaher, Schütte, André, Gustafsson, Jenny K., Ermund, Anna, Subramani, Durai B., Holmén-Larsson, Jessica M., Thomsson, Kristina A., Bergström, Joakim H., van der Post, Sjoerd, Rodriguez-Piñeiro, Ana M., Sjövall, Henrik, Bäckström, Malin, and Hansson, Gunnar C.
- Published
- 2011
- Full Text
- View/download PDF
6. The gastric mucus layers : constituents and regulation of accumulation
- Author
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Phillipson, Mia, Johansson, Malin E V, Henriksnäs, Johanna, Petersson, Joel, Gendler, Sandra J, Sandler, Stellan, Persson, A Erik G, Hansson, Gunnar C, Holm, Lena, Phillipson, Mia, Johansson, Malin E V, Henriksnäs, Johanna, Petersson, Joel, Gendler, Sandra J, Sandler, Stellan, Persson, A Erik G, Hansson, Gunnar C, and Holm, Lena
- Abstract
The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1-/-, inducible nitric oxide synthase (iNOS)-/-, and neuronal NOS (nNOS)-/-] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE(2) increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1-/- mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE(2) and NO. A new gastroprotective role for iNOS was indicated since iNOS-/- mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1-/- mice.
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- 2008
- Full Text
- View/download PDF
7. High-temperature effects on the mucus layers in a realistic human upper airway model
- Author
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Kulkarni, Nilay Atul, primary and Kleinstreuer, Clement, additional
- Published
- 2020
- Full Text
- View/download PDF
8. Fast renewal of the distal colonic mucus layers by the surface goblet cells as measured by in vivo labeling of mucin glycoproteins.
- Author
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Malin E V Johansson
- Subjects
Medicine ,Science - Abstract
The enormous bacterial load and mechanical forces in colon create a special requirement for protection of the epithelium. In the distal colon, this problem is largely solved by separation of the bacteria from the epithelium by a firmly attached inner mucus layer. In addition, an outer mucus layer entraps bacteria to be cleared by distal transport. The mucus layers contain a network of Muc2 mucins as the main structural component. Here, the renewal rate of the inner protective mucus layer was studied as well as the production and secretion of Muc2 mucin in the distal colon. This was performed by intraperitoneal injection of N-azidoacetyl-galactosamine (GalNAz) that was in vivo incorporated during biosynthesis of O-glycosylated glycoproteins. The only gel-forming mucin produced in the colon is the Muc2 mucin and as it carries numerous O-glycans, the granulae of the goblet cells producing Muc2 mucin were intensely stained. The GalNAz-labeled glycoproteins were first observed in the Golgi apparatus of most cells. Goblet cells in the luminal surface epithelium had the fastest biosynthesis of Muc2 and secreted material already three hours after labeling. This secreted GalNAz-labeled Muc2 mucin formed the inner mucus layer. The goblet cells along the crypt epithelium accumulated labeled mucin vesicles for a longer period and secretion of labeled Muc2 mucin was first observed after 6 to 8 h. This study reveals a fast turnover (1 h) of the inner mucus layer in the distal colon mediated by goblet cells of the luminal surface epithelium.
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- 2012
- Full Text
- View/download PDF
9. The rat IgGFcγBP and Muc2 C-terminal domains and TFF3 in two intestinal mucus layers bind together by covalent interaction.
- Author
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Hao Yu, Yonghong He, Xin Zhang, Zhihong Peng, Yongtao Yang, Rong Zhu, Jianying Bai, Yin Tian, Xiaohuan Li, Wensheng Chen, Dianchun Fang, and Rongquan Wang
- Subjects
Medicine ,Science - Abstract
The secreted proteins from goblet cells compose the intestinal mucus. The aims of this study were to determine how they exist in two intestinal mucus layers.The intestinal mucosa was fixed with Carnoy solution and immunostained. Mucus from the loose layer, the firm layer was gently suctioned or scraped, respectively, lysed in SDS sample buffer with or without DTT, then subjected to the western blotting of rTFF3, rIgGFcγBP or rMuc2. The non-reduced or reduced soluble mucus samples in RIPA buffer were co-immunoprecipitated to investigate their possible interactions. Polyclonal antibodies for rTFF3, the rIgGFcγBP C-terminal domain and the rMuc2 C-terminal domain confirmed their localization in the mucus layer and in the mucus collected from the rat intestinal loose layer or firm layer in both western blot and immunoprecipitation experiments. A complex of rTFF3, which was approximately 250 kDa, and a monomer of 6 kDa were present in both layers of the intestinal mucus; rIgGFcγBP was present in the complex (250-280 kDa) under non-reducing conditions, but shifted to 164 kDa under reducing conditions in both of the layers. rMuc2 was found mainly in a complex of 214-270 kDa under non-reducing conditions, but it shifted to 140 kDa under reducing conditions. The co-immunoprecipitation experiments showed that binding occurs among rTFF3, rIgGFcγBP and rMuc2 in the RIPA buffer soluble intestinal mucus. Blocking the covalent interaction by 100 mM DTT in the RIPA buffer soluble intestinal mucus disassociated their binding.Rat goblet cell-secreted TFF3, IgGFcγBP and Muc2, existing in the two intestinal mucus layers, are bound together by covalent interactions in the soluble fraction of intestinal mucus and form heteropolymers to be one of the biochemical mechanisms of composing the net-like structure of mucus.
- Published
- 2011
- Full Text
- View/download PDF
10. Normalization of Host Intestinal Mucus Layers Requires Long-Term Microbial Colonization.
- Author
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Johansson, Malin E.V., Jakobsson, Hedvig E., Holmén-Larsson, Jessica, Schütte, André, Ermund, Anna, Rodríguez-Piñeiro, Ana M., Arike, Liisa, Wising, Catharina, Svensson, Frida, Bäckhed, Fredrik, and Hansson, Gunnar C.
- Abstract
Summary The intestinal mucus layer provides a barrier limiting bacterial contact with the underlying epithelium. Mucus structure is shaped by intestinal location and the microbiota. To understand how commensals modulate gut mucus, we examined mucus properties under germ-free (GF) conditions and during microbial colonization. Although the colon mucus organization of GF mice was similar to that of conventionally raised (Convr) mice, the GF inner mucus layer was penetrable to bacteria-sized beads. During colonization, in which GF mice were gavaged with Convr microbiota, the small intestine mucus required 5 weeks to be normally detached and colonic inner mucus 6 weeks to become impenetrable. The composition of the small intestinal microbiota during colonization was similar to Convr donors until 3 weeks, when Bacteroides increased, Firmicutes decreased, and segmented filamentous bacteria became undetectable. These findings highlight the dynamics of mucus layer development and indicate that studies of mature microbe-mucus interactions should be conducted weeks after colonization. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
11. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
- Author
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Hansson, Gunnar C. and Johansson, Malin E.V.
- Published
- 2010
12. Cover 2 - Making Functional Mucus Layers In Vitro (cover)
- Published
- 2019
- Full Text
- View/download PDF
13. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
- Author
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Johansson, Malin E V, Phillipson, Mia, Petersson, Joel, Velcich, Anna, Holm, Lena, Hansson, Gunnar C, Johansson, Malin E V, Phillipson, Mia, Petersson, Joel, Velcich, Anna, Holm, Lena, and Hansson, Gunnar C
- Abstract
We normally live in symbiosis with approximately 10(13) bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is limited understanding of the structure, function, and properties of intestinal mucus. We now demonstrate that the mouse colonic mucus consists of two layers extending 150 mum above the epithelial cells. Proteomics revealed that both of these layers have similar protein composition, with the large gel-forming mucin Muc2 as the major structural component. The inner layer is densely packed, firmly attached to the epithelium, and devoid of bacteria. In contrast, the outer layer is movable, has an expanded volume due to proteolytic cleavages of the Muc2 mucin, and is colonized by bacteria. Muc2(-/-) mice have bacteria in direct contact with the epithelial cells and far down in the crypts, explaining the inflammation and cancer development observed in these animals. These findings show that the Muc2 mucin can build a mucus barrier that separates bacteria from the colon epithelia and suggest that defects in this mucus can cause colon inflammation.
- Published
- 2008
- Full Text
- View/download PDF
14. High-temperature effects on the mucus layers in a realistic human upper airway model
- Author
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Clement Kleinstreuer and Nilay Atul Kulkarni
- Subjects
Fluid Flow and Transfer Processes ,Materials science ,Convective heat transfer ,Mechanical Engineering ,Airflow ,02 engineering and technology ,Mechanics ,respiratory system ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Mucus ,010305 fluids & plasmas ,Volumetric flow rate ,Heat flux ,Mass transfer ,0103 physical sciences ,Shear stress ,Relative humidity ,0210 nano-technology - Abstract
Firefighters and workers in some industries often inhale (polluted) air at high temperatures, eg, 50–200°C, and very low relative humidity, say, 5–10%. Such severe environmental conditions may cause health problems or further aggravate existing ones. As in vivo tests are very complex, potentially harmful and costly, and in vitro experiments often lack high resolution and predictive capability, in silico studies become a priority. They may include computer simulations of the air-particle dynamics in human lung-airway models to understand the convection heat transfer as well as pollutant transport, deposition and uptake at high inlet temperatures and low relative humidity. In this study, detailed modeling, simulation and analysis focuses on two-phase flow in a human upper lung-airway model with a realistic 3D mucus lining. Especially modeling of the upper airway mucus layers was of interest in order to simulate the vapor mass transfer to the airflow because of its primary function for airway humidification. Naturally, the humidification causes water loss in the mucus layer, which leads to its reduction or even depletion when exposed to relatively high temperatures. Accounting for the changes in thickness and the rise in temperature in the mucus layer allows for the determination of locations of thermal injury in the human airways due to continuous exposure of such abnormal inhalation conditions. Different temperature profiles and local changes in mucus layer thickness were studied for ranges of severe inlet temperature conditions at a representative flow rate of 20 LPM (liters per minute). For inlet temperature reaching 100°C, mucus-layer thinning was observed in the upper airways. Interestingly, as a confirmation of the Reynolds analogy, the areas of significant wall heat flux and associated wall shear stress coincided with the regions of highest mucus evaporation, resulting in the humidification of the air with low relative humidity. Model development and mucus layer generation were done using C++ programming. All computer simulations were carried out using the open-source computational fluid dynamics toolbox OpenFOAM.
- Published
- 2020
- Full Text
- View/download PDF
15. The importance of mucus layers and bicarbonate transport in preservation of gastric juxtamucosal pH
- Author
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Phillipson, Mia, Atuma, Christer, Henriksnäs, Johanna, Holm, Lena, Phillipson, Mia, Atuma, Christer, Henriksnäs, Johanna, and Holm, Lena
- Abstract
Mucus thickness is suggested to be related to mucosal protection. We therefore investigated the importance of the removable mucous layer and epithelial bicarbonate transport in preservation of the gastric juxtamucosal pH (pH(jm)) during luminal acid. Anesthetized rats were prepared for intravital microscopy of the gastric mucosa, and pH(jm) was measured with pH-sensitive microelectrodes. The mucus was either left intact (IM) or removed (MR) down to the firmly attached mucous layer, and HCl (pH 1) was applied luminally. Removal of the loosely adherent mucous layer did not influence the pH(jm) during luminal acid (pentagastrin: IM/MR 7.03 +/- 0.09/6.82 +/- 0.19; pentagastrin + indomethacin: IM/MR 6.89 +/- 0.20/6.95 +/- 0.27; ranitidine: IM/MR 2.38 +/- 0.64/2.97 +/- 0.62), unless prostaglandin synthesis and acid secretion were inhibited (ranitidine + indomethacin: IM/MR 2.03 +/- 0.37/1.66 +/- 0.18). Neutral pH(jm) is maintained during endogenous acid secretion and luminal pH 1, unless DIDS was applied luminally, which resulted in a substantially decreased pH(jm) (1.37 +/- 0.21). Neutral pH(jm) is maintained by a DIDS-sensitive bicarbonate transport over the surface epithelium. The loosely adherent mucous layer only contributes to maintaining pH(jm) during luminal pH 1 if acid secretion and prostaglandin synthesis are inhibited.
- Published
- 2002
- Full Text
- View/download PDF
16. The importance of mucus layers and bicarbonate transport in preservationof gastric juxtamucosal pH.
- Author
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Phillipson, M, Atuma, C, Henriksnas, J, Holm, L, Phillipson, M, Atuma, C, Henriksnas, J, and Holm, L
- Published
- 2002
17. Survey of Antibiotic-producing Bacteria Associated with the Epidermal Mucus Layers of Rays and Skates.
- Author
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Ritchie KB, Schwarz M, Mueller J, Lapacek VA, Merselis D, Walsh CJ, and Luer CA
- Abstract
Elasmobranchs represent a distinct group of cartilaginous fishes that harbor a remarkable ability to heal wounds rapidly and without infection. To date very little work has addressed this phenomenon although it is suggested that antibiotic capabilities associated with epidermal surfaces may be a factor. The study of benefits derived from mutualistic interactions between unicellular and multicellular organisms is a rapidly growing area of research. Here we survey and identify bacterial associates of three ray and one skate species in order to assess the potential for antibiotic production from elasmobranch associated bacteria as a novel source for new antibiotics.
- Published
- 2017
- Full Text
- View/download PDF
18. Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice
- Author
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Chen Y, Qi Wang, Tao Liao, Li-Li Tan, Qin Xu, Qing-Ping Zeng, Shui-Qing Huang, Chang-Qing Li, and Xin-An Huang
- Subjects
biology ,Lipopolysaccharide ,Mucin ,Arthritis ,Inflammation ,Gut flora ,biology.organism_classification ,medicine.disease ,Systemic inflammation ,Mucus ,Microbiology ,Pathogenesis ,chemistry.chemical_compound ,chemistry ,Immunology ,medicine ,medicine.symptom - Abstract
BackgroundAn interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containing O-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks.ResultsA metagenomic gut microbiota analysis revealed the overgrowth of sulfatase-secreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor α (TNF-α) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver.ConclusionsCS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.
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- 2017
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19. Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon
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Maria Arampatzidou, Paul Saftig, Gunnar C. Hansson, André Schütte, and Klaudia Brix
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Male ,Colon ,Cathepsin L ,Cathepsin K ,Clinical Biochemistry ,Biochemistry ,Article ,Cathepsin B ,Mice ,Cathepsin O ,Cathepsin H ,Occludin ,Cathepsin L1 ,Animals ,Intestinal Mucosa ,Molecular Biology ,Cathepsin S ,Cathepsin ,biology ,Cadherins ,Extracellular Matrix ,Cell biology ,Mice, Inbred C57BL ,Intercellular Junctions ,Proteolysis ,biology.protein ,Gene Deletion - Abstract
Cathepsin K has been shown to exhibit antimicrobial and anti-inflammatory activities in the mouse colon. To further elucidate its role, we used Ctsk -/- mice and demonstrated that the absence of cathepsin K was accompanied by elevated protein levels of related cysteine cathepsins (cathepsins B, L, and X) in the colon. In principle, such changes could result in altered subcellular localization; however, the trafficking of cysteine cathepsins was not affected in the colon of Ctsk -/- mice. However, cathepsin K deficiency affected the extracellular matrix constituents, as higher amounts of collagen IV and laminin were observed. Moreover, the localization pattern of the intercellular junction proteins E-cadherin and occludin was altered in the colon of Ctsk -/- mice, suggesting potential impairment of the barrier function. Thus, we used an ex vivo method for assessing the mucus layers and showed that the absence of cathepsin K had no influence on mucus organization and growth. The data of this study support the notion that cathepsin K contributes to intestinal homeostasis and tissue architecture, but the lack of cathepsin K activity is not expected to affect the mucus-depending barrier functions of the mouse colon. These results are important with regard to oral administration of cathepsin K inhibitors that are currently under investigation in clinical trials.
- Published
- 2012
- Full Text
- View/download PDF
20. Survey of Antibiotic-producing Bacteria Associated with the Epidermal Mucus Layers of Rays and Skates
- Author
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Catherine J. Walsh, Daniel G. Merselis, Valeri A. Lapacek, Joseph Mueller, Melbert T. Schwarz, Carl A. Luer, and Kim B. Ritchie
- Subjects
0106 biological sciences ,0301 basic medicine ,Microbiology (medical) ,antibacterial screening ,medicine.drug_class ,Antibiotics ,lcsh:QR1-502 ,01 natural sciences ,Microbiology ,lcsh:Microbiology ,03 medical and health sciences ,Beneficial bacteria ,medicine ,epidermal mucus ,Skate ,beneficial bacteria ,Original Research ,biology ,stingray ,010604 marine biology & hydrobiology ,skate ,pathogens ,Antibiotic production ,biology.organism_classification ,Mucus ,Multicellular organism ,antibiotic producing bacteria ,030104 developmental biology ,Associated bacteria ,Bacteria - Abstract
Elasmobranchs represent a distinct group of cartilaginous fishes that harbor a remarkable ability to heal wounds rapidly and without infection. To date very little work has addressed this phenomenon although it is suggested that antibiotic capabilities associated with epidermal surfaces may be a factor. The study of benefits derived from mutualistic interactions between unicellular and multicellular organisms is a rapidly growing area of research. Here we survey and identify bacterial associates of three ray and one skate species in order to assess the potential for antibiotic production from elasmobranch associated bacteria as a novel source for new antibiotics.
- Published
- 2016
21. Role of mucus layers in gut infection and inflammation
- Author
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Gunnar C. Hansson
- Subjects
Microbiology (medical) ,Inflammation ,Biology ,Microbiology ,Article ,Enteritis ,03 medical and health sciences ,0302 clinical medicine ,fluids and secretions ,Intestinal mucosa ,medicine ,Animals ,Humans ,Intestinal Mucosa ,030304 developmental biology ,Inner mucus layer ,0303 health sciences ,Gastrointestinal tract ,Bacteria ,Bacterial Infections ,respiratory system ,biology.organism_classification ,medicine.disease ,Mucus ,Epithelium ,3. Good health ,Gastrointestinal Tract ,Infectious Diseases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,medicine.symptom - Abstract
The intestinal mucus is an efficient system for protecting the epithelium from bacteria by promoting their clearance and separating them from the epithelial cells, thereby inhibiting inflammation and infection. The function of the colon inner mucus layer is especially important as this explains how we can harbor the large number of bacteria in our gut. The major component of this mucus system is the MUC2 mucin which organizes the mucus by its enormously large net-like polymers. Pathogenic microorganisms, in turn, have developed mechanisms for circumventing this well-organized mucus protective system.
- Published
- 2012
- Full Text
- View/download PDF
22. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
- Author
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Malin E. V. Johansson and Gunnar C. Hansson
- Subjects
Microbiology (medical) ,Muc2 mucin ,Gastroenterology ,Colon inflammation ,respiratory system ,Biology ,biology.organism_classification ,Microbiology ,Mucus ,digestive system diseases ,Article Addendum ,fluids and secretions ,Infectious Diseases ,sense organs ,Bacteria ,Inner mucus layer - Abstract
We have recently shown that the colon is protected by an inner mucus layer that efficiently separates the bacteria in the outer mucus from the epithelial cells. The inner mucus is impervious for bacteria and built by a network formed by the MUC2 mucin. Lack or defects in this inner mucus layer allow bacteria to reach the epithelia, something that triggers colon inflammation.
- Published
- 2010
- Full Text
- View/download PDF
23. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
- Author
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Mia Phillipson, Malin E. V. Johansson, Joel Petersson, Anna Velcich, Lena Holm, and Gunnar C. Hansson
- Subjects
Colon ,Mucin 2 ,Biology ,Microbiology ,Rats, Sprague-Dawley ,Mice ,Intestinal mucosa ,medicine ,Animals ,Large intestine ,Intestinal Mucosa ,Symbiosis ,Outer mucus layer ,Inner mucus layer ,Mucin-2 ,Multidisciplinary ,Mucin ,Mucins ,Bacteria Present ,Biological Sciences ,respiratory system ,Colitis ,Mucus ,Mice, Mutant Strains ,digestive system diseases ,Rats ,medicine.anatomical_structure - Abstract
We normally live in symbiosis with ∼10 13 bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is limited understanding of the structure, function, and properties of intestinal mucus. We now demonstrate that the mouse colonic mucus consists of two layers extending 150 μm above the epithelial cells. Proteomics revealed that both of these layers have similar protein composition, with the large gel-forming mucin Muc2 as the major structural component. The inner layer is densely packed, firmly attached to the epithelium, and devoid of bacteria. In contrast, the outer layer is movable, has an expanded volume due to proteolytic cleavages of the Muc2 mucin, and is colonized by bacteria. Muc2 −/− mice have bacteria in direct contact with the epithelial cells and far down in the crypts, explaining the inflammation and cancer development observed in these animals. These findings show that the Muc2 mucin can build a mucus barrier that separates bacteria from the colon epithelia and suggest that defects in this mucus can cause colon inflammation.
- Published
- 2008
- Full Text
- View/download PDF
24. Normalization of Host Intestinal Mucus Layers Requires Long-Term Microbial Colonization
- Author
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Hedvig E. Jakobsson, Gunnar C. Hansson, Catharina Wising, Ana M. Rodríguez-Piñeiro, André Schütte, Jessica Holmén-Larsson, Frida Svensson, Liisa Arike, Malin E. V. Johansson, Fredrik Bäckhed, and Anna Ermund
- Subjects
Cancer Research ,Segmented filamentous bacteria ,Firmicutes ,Mucin 2 ,Gut flora ,digestive system ,Microbiology ,Article ,Mice ,fluids and secretions ,Intestinal mucosa ,Immunology and Microbiology(all) ,Virology ,medicine ,Animals ,Bacteroides ,Germ-Free Life ,Intestinal Mucosa ,Molecular Biology ,Inner mucus layer ,Mucin-2 ,biology ,Mucin ,Bacterial Infections ,respiratory system ,biology.organism_classification ,Mucus ,digestive system diseases ,Small intestine ,Gastrointestinal Microbiome ,medicine.anatomical_structure ,Parasitology - Abstract
SummaryThe intestinal mucus layer provides a barrier limiting bacterial contact with the underlying epithelium. Mucus structure is shaped by intestinal location and the microbiota. To understand how commensals modulate gut mucus, we examined mucus properties under germ-free (GF) conditions and during microbial colonization. Although the colon mucus organization of GF mice was similar to that of conventionally raised (Convr) mice, the GF inner mucus layer was penetrable to bacteria-sized beads. During colonization, in which GF mice were gavaged with Convr microbiota, the small intestine mucus required 5 weeks to be normally detached and colonic inner mucus 6 weeks to become impenetrable. The composition of the small intestinal microbiota during colonization was similar to Convr donors until 3 weeks, when Bacteroides increased, Firmicutes decreased, and segmented filamentous bacteria became undetectable. These findings highlight the dynamics of mucus layer development and indicate that studies of mature microbe-mucus interactions should be conducted weeks after colonization.
- Published
- 2015
25. Fast Renewal of the Distal Colonic Mucus Layers by the Surface Goblet Cells as Measured by In Vivo Labeling of Mucin Glycoproteins.
- Author
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Johansson, Malin E. V.
- Subjects
- *
GLYCOPROTEINS , *EPITHELIUM , *PROTEINS , *GALACTOSAMINE , *BIOSYNTHESIS - Abstract
The enormous bacterial load and mechanical forces in colon create a special requirement for protection of the epithelium. In the distal colon, this problem is largely solved by separation of the bacteria from the epithelium by a firmly attached inner mucus layer. In addition, an outer mucus layer entraps bacteria to be cleared by distal transport. The mucus layers contain a network of Muc2 mucins as the main structural component. Here, the renewal rate of the inner protective mucus layer was studied as well as the production and secretion of Muc2 mucin in the distal colon. This was performed by intraperitoneal injection of N-azidoacetyl-galactosamine (GalNAz) that was in vivo incorporated during biosynthesis of O-glycosylated glycoproteins. The only gel-forming mucin produced in the colon is the Muc2 mucin and as it carries numerous O-glycans, the granulae of the goblet cells producing Muc2 mucin were intensely stained. The GalNAz-labeled glycoproteins were first observed in the Golgi apparatus of most cells. Goblet cells in the luminal surface epithelium had the fastest biosynthesis of Muc2 and secreted material already three hours after labeling. This secreted GalNAz-labeled Muc2 mucin formed the inner mucus layer. The goblet cells along the crypt epithelium accumulated labeled mucin vesicles for a longer period and secretion of labeled Muc2 mucin was first observed after 6 to 8 h. This study reveals a fast turnover (1 h) of the inner mucus layer in the distal colon mediated by goblet cells of the luminal surface epithelium. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
26. Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches.
- Author
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Ermund A, Schütte A, Johansson ME, Gustafsson JK, and Hansson GC
- Subjects
- Adhesiveness, Animals, Carbachol pharmacology, Colon drug effects, Colon microbiology, Dinoprostone pharmacology, Female, Fluorescent Dyes metabolism, Gastric Mucosa drug effects, Gastric Mucosa microbiology, Intestinal Absorption, Intestinal Mucosa drug effects, Intestinal Mucosa microbiology, Intestine, Small drug effects, Intestine, Small microbiology, Male, Mice, Mice, Inbred C57BL, Microscopy, Confocal, Microscopy, Video, Mucus microbiology, Permeability, Peyer's Patches drug effects, Time Factors, Colon metabolism, Gastric Mucosa metabolism, Intestinal Mucosa metabolism, Intestine, Small metabolism, Mucus metabolism, Peyer's Patches metabolism
- Abstract
Colon has been shown to have a two-layered mucus system where the inner layer is devoid of bacteria. However, a complete overview of the mouse gastrointestinal mucus system is lacking. We now characterize mucus release, thickness, growth over time, adhesive properties, and penetrability to fluorescent beads from stomach to distal colon. Colon displayed spontaneous mucus release and all regions released mucus in response to carbachol and PGE2, except the distal colon and domes of Peyer's patches. Stomach and colon had an inner mucus layer that was adherent to the epithelium. In contrast, the small intestine and Peyer's patches had a single mucus layer that was easily aspirated. The inner mucus layer of the distal colon was not penetrable to beads the size of bacteria and the inner layer of the proximal colon was only partly penetrable. In contrast, the inner mucus layer of stomach was fully penetrable, as was the small intestinal mucus. This suggests a functional organization of the intestinal mucus system, where the small intestine has loose and penetrable mucus that may allow easy penetration of nutrients, in contrast to the stomach, where the mucus provides physical protection, and the colon, where the mucus separates bacteria from the epithelium. This knowledge of the mucus system and its organization improves our understanding of the gastrointestinal tract physiology.
- Published
- 2013
- Full Text
- View/download PDF
27. The gastric mucus layers: constituents and regulation of accumulation
- Author
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Gunnar C. Hansson, Stellan Sandler, Malin E. V. Johansson, Lena Holm, A. Erik G. Persson, Sandra J. Gendler, Johanna Henriksnäs, Mia Phillipson, and Joel Petersson
- Subjects
Male ,Physiology ,Indomethacin ,Molecular Sequence Data ,Nitric Oxide Synthase Type II ,Biology ,S-Nitroso-N-Acetylpenicillamine ,Nitric Oxide ,Dinoprostone ,Nitric oxide ,chemistry.chemical_compound ,fluids and secretions ,Physiology (medical) ,medicine ,Gastric mucosa ,Animals ,Amino Acid Sequence ,Intestinal Mucosa ,Hepatology ,Stomach ,Mucin ,Mucin-1 ,Gastroenterology ,respiratory system ,Molecular biology ,Mucus ,Epithelium ,Rats ,Nitric oxide synthase ,medicine.anatomical_structure ,chemistry ,Eicosanoid ,Biochemistry ,biology.protein ,Female - Abstract
The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1−/−, inducible nitric oxide synthase (iNOS)−/−, and neuronal NOS (nNOS)−/−] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE2increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1−/− mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE2and NO. A new gastroprotective role for iNOS was indicated since iNOS−/− mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1−/− mice.
- Published
- 2008
28. Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches
- Author
-
André Schütte, Malin E. V. Johansson, Jenny K. Gustafsson, Anna Ermund, and Gunnar C. Hansson
- Subjects
Male ,Time Factors ,Physiology ,Colon ,Biology ,Intestinal absorption ,Dinoprostone ,Permeability ,Mice ,Peyer's Patches ,fluids and secretions ,Intestinal mucosa ,Mucosal Biology ,Physiology (medical) ,Intestine, Small ,medicine ,Gastric mucosa ,Animals ,Intestinal Mucosa ,Inner mucus layer ,Fluorescent Dyes ,Microscopy, Confocal ,Microscopy, Video ,Hepatology ,Stomach ,Mucin ,Gastroenterology ,Adhesiveness ,Anatomy ,respiratory system ,Mucus ,Small intestine ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Intestinal Absorption ,Gastric Mucosa ,Carbachol ,Female - Abstract
Colon has been shown to have a two-layered mucus system where the inner layer is devoid of bacteria. However, a complete overview of the mouse gastrointestinal mucus system is lacking. We now characterize mucus release, thickness, growth over time, adhesive properties, and penetrability to fluorescent beads from stomach to distal colon. Colon displayed spontaneous mucus release and all regions released mucus in response to carbachol and PGE2, except the distal colon and domes of Peyer's patches. Stomach and colon had an inner mucus layer that was adherent to the epithelium. In contrast, the small intestine and Peyer's patches had a single mucus layer that was easily aspirated. The inner mucus layer of the distal colon was not penetrable to beads the size of bacteria and the inner layer of the proximal colon was only partly penetrable. In contrast, the inner mucus layer of stomach was fully penetrable, as was the small intestinal mucus. This suggests a functional organization of the intestinal mucus system, where the small intestine has loose and penetrable mucus that may allow easy penetration of nutrients, in contrast to the stomach, where the mucus provides physical protection, and the colon, where the mucus separates bacteria from the epithelium. This knowledge of the mucus system and its organization improves our understanding of the gastrointestinal tract physiology.
- Published
- 2013
29. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions
- Author
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Malin E. V. Johansson, Gunnar C. Hansson, and Jessica M. Holmén Larsson
- Subjects
Mucin-2 ,Multidisciplinary ,Glycosylation ,biology ,Colon ,Colloquium Papers ,Mucin 2 ,respiratory system ,biology.organism_classification ,Mucus ,Models, Biological ,Microbiology ,Mice ,Intestinal mucosa ,Anatomy & histology ,Animals ,Humans ,Metagenome ,Secretion ,Goblet Cells ,Intestinal Mucosa ,Outer mucus layer ,Symbiosis ,Bacteria ,Inner mucus layer - Abstract
The normal intestinal microbiota inhabits the colon mucus without triggering an inflammatory response. The reason for this and how the intestinal mucus of the colon is organized have begun to be unraveled. The mucus is organized in two layers: an inner, stratified mucus layer that is firmly adherent to the epithelial cells and approximately 50 μm thick; and an outer, nonattached layer that is usually approximately 100 μm thick as measured in mouse. These mucus layers are organized around the highly glycosylated MUC2 mucin, forming a large, net-like polymer that is secreted by the goblet cells. The inner mucus layer is dense and does not allow bacteria to penetrate, thus keeping the epithelial cell surface free from bacteria. The inner mucus layer is converted into the outer layer, which is the habitat of the commensal flora. The outer mucus layer has an expanded volume due to proteolytic activities provided by the host but probably also caused by commensal bacterial proteases and glycosidases. The numerous O -glycans on the MUC2 mucin not only serve as nutrients for the bacteria but also as attachment sites and, as such, probably contribute to the selection of the species-specific colon flora. This observation that normal human individuals carry a uniform MUC2 mucin glycan array in colon may indicate such a specific selection.
- Published
- 2010
30. The rat IgGFcγBP and Muc2 C-terminal domains and TFF3 in two intestinal mucus layers bind together by covalent interaction.
- Author
-
Yu H, He Y, Zhang X, Peng Z, Yang Y, Zhu R, Bai J, Tian Y, Li X, Chen W, Fang D, and Wang R
- Subjects
- Animals, Blotting, Western, Electrophoresis, Polyacrylamide Gel, Goblet Cells metabolism, Immunohistochemistry, Immunoprecipitation, In Vitro Techniques, Mucin-2 genetics, Mucins genetics, Neuropeptides genetics, Protein Binding, Rats, Rats, Wistar, Trefoil Factor-3, Intestinal Mucosa metabolism, Mucin-2 metabolism, Mucins metabolism, Neuropeptides metabolism
- Abstract
Background: The secreted proteins from goblet cells compose the intestinal mucus. The aims of this study were to determine how they exist in two intestinal mucus layers., Methodology/principal Findings: The intestinal mucosa was fixed with Carnoy solution and immunostained. Mucus from the loose layer, the firm layer was gently suctioned or scraped, respectively, lysed in SDS sample buffer with or without DTT, then subjected to the western blotting of rTFF3, rIgGFcγBP or rMuc2. The non-reduced or reduced soluble mucus samples in RIPA buffer were co-immunoprecipitated to investigate their possible interactions. Polyclonal antibodies for rTFF3, the rIgGFcγBP C-terminal domain and the rMuc2 C-terminal domain confirmed their localization in the mucus layer and in the mucus collected from the rat intestinal loose layer or firm layer in both western blot and immunoprecipitation experiments. A complex of rTFF3, which was approximately 250 kDa, and a monomer of 6 kDa were present in both layers of the intestinal mucus; rIgGFcγBP was present in the complex (250-280 kDa) under non-reducing conditions, but shifted to 164 kDa under reducing conditions in both of the layers. rMuc2 was found mainly in a complex of 214-270 kDa under non-reducing conditions, but it shifted to 140 kDa under reducing conditions. The co-immunoprecipitation experiments showed that binding occurs among rTFF3, rIgGFcγBP and rMuc2 in the RIPA buffer soluble intestinal mucus. Blocking the covalent interaction by 100 mM DTT in the RIPA buffer soluble intestinal mucus disassociated their binding., Conclusions/significance: Rat goblet cell-secreted TFF3, IgGFcγBP and Muc2, existing in the two intestinal mucus layers, are bound together by covalent interactions in the soluble fraction of intestinal mucus and form heteropolymers to be one of the biochemical mechanisms of composing the net-like structure of mucus.
- Published
- 2011
- Full Text
- View/download PDF
31. Drug Delivery Across Mucus Layers: Are We Getting the Whole Picture?
- Author
-
Dmitri V Nikitin
- Subjects
Drug ,media_common.quotation_subject ,Biology ,Pharmacology ,Anticancer drug ,Yeast ,media_common - Published
- 2012
- Full Text
- View/download PDF
32. Cover 2 - Making Functional Mucus Layers In Vitro (cover)
- Published
- 2019
- Full Text
- View/download PDF
33. Composition and functional role of the mucus layers in the intestine
- Author
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André Schütte, Jenny K. Gustafsson, Malin E. V. Johansson, Joakim H. Bergström, Durai B. Subramani, Anna Ermund, Thaher Pelaseyed, Daniel Ambort, Gunnar C. Hansson, Malin Bäckström, Jessica Holmén-Larsson, Ana M. Rodríguez-Piñeiro, Kristina A. Thomsson, Henrik Sjövall, and Sjoerd van der Post
- Subjects
Functional role ,Models, Molecular ,Protective capacity ,Microbiology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,fluids and secretions ,0302 clinical medicine ,medicine ,Animals ,Humans ,Large intestine ,Intestinal Mucosa ,Molecular Biology ,Immunity, Mucosal ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Chemistry ,Mucin ,Mucins ,Cell Biology ,respiratory system ,Mucus ,Small intestine ,Transmembrane protein ,Cell biology ,Intestines ,medicine.anatomical_structure ,Enterocytes ,Mucosal immunology ,030220 oncology & carcinogenesis ,Molecular Medicine - Abstract
In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.
- Published
- 2011
34. The gastric mucus layers: constituents and regulation of accumulation.
- Author
-
Phillipson M, Johansson ME, Henriksnäs J, Petersson J, Gendler SJ, Sandler S, Persson AE, Hansson GC, and Holm L
- Subjects
- Amino Acid Sequence, Animals, Dinoprostone pharmacology, Female, Indomethacin pharmacology, Intestinal Mucosa drug effects, Male, Molecular Sequence Data, Nitric Oxide physiology, Nitric Oxide Synthase Type II antagonists & inhibitors, Nitric Oxide Synthase Type II physiology, Rats, S-Nitroso-N-Acetylpenicillamine pharmacology, Intestinal Mucosa chemistry, Mucin-1 physiology, Mucus metabolism
- Abstract
The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1-/-, inducible nitric oxide synthase (iNOS)-/-, and neuronal NOS (nNOS)-/-] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE(2) increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1-/- mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE(2) and NO. A new gastroprotective role for iNOS was indicated since iNOS-/- mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1-/- mice.
- Published
- 2008
- Full Text
- View/download PDF
35. Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches
- Author
-
Ermund, Anna, primary, Schütte, André, additional, Johansson, Malin E. V., additional, Gustafsson, Jenny K., additional, and Hansson, Gunnar C., additional
- Published
- 2013
- Full Text
- View/download PDF
36. Drug Delivery Across Mucus Layers: Are We Getting the Whole Picture?
- Author
-
Picher, Maryse, primary
- Published
- 2012
- Full Text
- View/download PDF
37. The importance of mucus layers and bicarbonate transport in preservation of gastric juxtamucosal pH.
- Author
-
Phillipson M, Atuma C, Henriksnäs J, and Holm L
- Subjects
- 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid pharmacology, Animals, Anti-Ulcer Agents pharmacology, Biological Transport drug effects, Biological Transport physiology, Chloride-Bicarbonate Antiporters metabolism, Cyclooxygenase Inhibitors pharmacology, Indomethacin pharmacology, Male, Pentagastrin pharmacology, Ranitidine pharmacology, Rats, Rats, Sprague-Dawley, Bicarbonates metabolism, Gastric Acid metabolism, Gastric Mucosa metabolism, Hydrogen-Ion Concentration drug effects
- Abstract
Mucus thickness is suggested to be related to mucosal protection. We therefore investigated the importance of the removable mucous layer and epithelial bicarbonate transport in preservation of the gastric juxtamucosal pH (pH(jm)) during luminal acid. Anesthetized rats were prepared for intravital microscopy of the gastric mucosa, and pH(jm) was measured with pH-sensitive microelectrodes. The mucus was either left intact (IM) or removed (MR) down to the firmly attached mucous layer, and HCl (pH 1) was applied luminally. Removal of the loosely adherent mucous layer did not influence the pH(jm) during luminal acid (pentagastrin: IM/MR 7.03 +/- 0.09/6.82 +/- 0.19; pentagastrin + indomethacin: IM/MR 6.89 +/- 0.20/6.95 +/- 0.27; ranitidine: IM/MR 2.38 +/- 0.64/2.97 +/- 0.62), unless prostaglandin synthesis and acid secretion were inhibited (ranitidine + indomethacin: IM/MR 2.03 +/- 0.37/1.66 +/- 0.18). Neutral pH(jm) is maintained during endogenous acid secretion and luminal pH 1, unless DIDS was applied luminally, which resulted in a substantially decreased pH(jm) (1.37 +/- 0.21). Neutral pH(jm) is maintained by a DIDS-sensitive bicarbonate transport over the surface epithelium. The loosely adherent mucous layer only contributes to maintaining pH(jm) during luminal pH 1 if acid secretion and prostaglandin synthesis are inhibited.
- Published
- 2002
- Full Text
- View/download PDF
38. Preparation, Drug Distribution, and In Vivo Evaluation of the Safety of Protein Corona Liposomes for Liraglutide Delivery
- Author
-
Ruihuan Ding, Zhenyu Zhao, Jibiao He, Yuping Tao, Houqian Zhang, Ranran Yuan, Kaoxiang Sun, and Yanan Shi
- Subjects
liposome ,oral drug delivery systems ,osmoregulatory peptide ,mucus layers ,intestinal epithelial permeability ,Chemistry ,QD1-999 - Abstract
The development of oral drug delivery systems is challenging, and issues related to the mucus layer and low intestinal epithelial permeability have not yet been surmounted. The purpose of this study was to develop a promising formulation that is more adapted to in vivo absorption and to facilitate the administration of oral liraglutide. Cationic liposomes (CLs) linked to AT-1002 were prepared using a double-emulsion method, and BSA was adsorbed on the surface of the AT-CLs, resulting in protein corona cationic liposomes with AT-1002 (Pc-AT-CLs). The preparation method was determined by investigating various process parameters. The particle size, potential, and encapsulation efficiency (EE%) of the Pc-AT-CLs were 202.9 ± 12.4 nm, 1.76 ± 4.87 mV, and 84.63 ± 5.05%, respectively. The transmission electron microscopy (TEM) imaging revealed a nearly spherical structure of the Pc-AT-CLs, with a recognizable coating. The circular dichroism experiments confirmed that the complex preparation process did not affect the secondary structure of liraglutide. With the addition of BSA and AT-1002, the mucosal accumulation of the Pc-AT-CLs was nearly two times lower than that of the AT-CLs, and the degree of enteric metaplasia was 1.35 times higher than that of the PcCLs. The duration of the intestinal absorption of the Pc-AT-CLs was longer, offering remarkable biological safety.
- Published
- 2023
- Full Text
- View/download PDF
39. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host–microbial interactions
- Author
-
Johansson, Malin E. V., primary, Larsson, Jessica M. Holmén, additional, and Hansson, Gunnar C., additional
- Published
- 2010
- Full Text
- View/download PDF
40. The importance of mucus layers and bicarbonate transport in preservation of gastric juxtamucosal pH
- Author
-
Mia Phillipson, Lena Holm, Christer Atuma, and Johanna Henriksnäs
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Indomethacin ,4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid ,Ranitidine ,Gastric Acid ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,medicine ,Gastric mucosa ,Animals ,Cyclooxygenase Inhibitors ,Chloride-Bicarbonate Antiporters ,Hepatology ,Gastroenterology ,Bicarbonate transport ,Biological Transport ,Apical membrane ,Hydrogen-Ion Concentration ,Anti-Ulcer Agents ,Mucus ,Rats ,Pentagastrin ,Bicarbonates ,Endocrinology ,medicine.anatomical_structure ,chemistry ,DIDS ,Gastric Mucosa ,Gastric acid ,Intravital microscopy ,medicine.drug - Abstract
Mucus thickness is suggested to be related to mucosal protection. We therefore investigated the importance of the removable mucous layer and epithelial bicarbonate transport in preservation of the gastric juxtamucosal pH (pHjm) during luminal acid. Anesthetized rats were prepared for intravital microscopy of the gastric mucosa, and pHjmwas measured with pH-sensitive microelectrodes. The mucus was either left intact (IM) or removed (MR) down to the firmly attached mucous layer, and HCl (pH 1) was applied luminally. Removal of the loosely adherent mucous layer did not influence the pHjmduring luminal acid (pentagastrin: IM/MR 7.03 ± 0.09/6.82 ± 0.19; pentagastrin + indomethacin: IM/MR 6.89 ± 0.20/6.95 ± 0.27; ranitidine: IM/MR 2.38 ± 0.64/2.97 ± 0.62), unless prostaglandin synthesis and acid secretion were inhibited (ranitidine + indomethacin: IM/MR 2.03 ± 0.37/1.66 ± 0.18). Neutral pHjmis maintained during endogenous acid secretion and luminal pH 1, unless DIDS was applied luminally, which resulted in a substantially decreased pHjm(1.37 ± 0.21). Neutral pHjmis maintained by a DIDS-sensitive bicarbonate transport over the surface epithelium. The loosely adherent mucous layer only contributes to maintaining pHjmduring luminal pH 1 if acid secretion and prostaglandin synthesis are inhibited.
- Published
- 2002
41. The Rat IgGFcγBP and Muc2 C-Terminal Domains and TFF3 in Two Intestinal Mucus Layers Bind Together by Covalent Interaction
- Author
-
Xin Zhang, Zhihong Peng, Yongtao Yang, Hao Yu, Jianying Bai, Rong Zhu, Dian-Chun Fang, Rongquan Wang, Yonghong He, Yin Tian, Xiaohuan Li, and Wensheng Chen
- Subjects
Proteomics ,Pathology ,medicine.medical_specialty ,Colon ,Blotting, Western ,lcsh:Medicine ,Gastroenterology and Hepatology ,Mucin 2 ,In Vitro Techniques ,Biochemistry ,Intestinal mucosa ,medicine ,Animals ,Immunoprecipitation ,Gastrointestinal Infections ,Intestinal Mucosa ,Rats, Wistar ,lcsh:Science ,Protein Interactions ,Biology ,Polyacrylamide gel electrophoresis ,Mucin-2 ,Multidisciplinary ,Chemistry ,lcsh:R ,Inflammatory Bowel Disease ,Neuropeptides ,Mucin ,Mucins ,Proteins ,respiratory system ,Immunohistochemistry ,Mucus ,Rats ,Blot ,Secretory protein ,Radioimmunoprecipitation assay buffer ,Medicine ,lcsh:Q ,Electrophoresis, Polyacrylamide Gel ,Goblet Cells ,Trefoil Factor-3 ,Research Article ,Protein Binding - Abstract
Background The secreted proteins from goblet cells compose the intestinal mucus. The aims of this study were to determine how they exist in two intestinal mucus layers. Methodology/Principal Findings The intestinal mucosa was fixed with Carnoy solution and immunostained. Mucus from the loose layer, the firm layer was gently suctioned or scraped, respectively, lysed in SDS sample buffer with or without DTT, then subjected to the western blotting of rTFF3, rIgGFcγBP or rMuc2. The non-reduced or reduced soluble mucus samples in RIPA buffer were co-immunoprecipitated to investigate their possible interactions. Polyclonal antibodies for rTFF3, the rIgGFcγBP C-terminal domain and the rMuc2 C-terminal domain confirmed their localization in the mucus layer and in the mucus collected from the rat intestinal loose layer or firm layer in both western blot and immunoprecipitation experiments. A complex of rTFF3, which was approximately 250 kDa, and a monomer of 6 kDa were present in both layers of the intestinal mucus; rIgGFcγBP was present in the complex (250–280 kDa) under non-reducing conditions, but shifted to 164 kDa under reducing conditions in both of the layers. rMuc2 was found mainly in a complex of 214–270 kDa under non-reducing conditions, but it shifted to 140 kDa under reducing conditions. The co-immunoprecipitation experiments showed that binding occurs among rTFF3, rIgGFcγBP and rMuc2 in the RIPA buffer soluble intestinal mucus. Blocking the covalent interaction by 100 mM DTT in the RIPA buffer soluble intestinal mucus disassociated their binding. Conclusions/Significance Rat goblet cell-secreted TFF3, IgGFcγBP and Muc2, existing in the two intestinal mucus layers, are bound together by covalent interactions in the soluble fraction of intestinal mucus and form heteropolymers to be one of the biochemical mechanisms of composing the net-like structure of mucus.
- Published
- 2011
- Full Text
- View/download PDF
42. The importance of mucus layers and bicarbonate transport in preservation of gastric juxtamucosal pH
- Author
-
Phillipson, Mia, primary, Atuma, Christer, additional, Henriksnäs, Johanna, additional, and Holm, Lena, additional
- Published
- 2002
- Full Text
- View/download PDF
43. Effects of prostaglandins on the two different gastric mucus layers in the anesthetized rat
- Author
-
Johansson, M., primary and Holm, L., additional
- Published
- 1998
- Full Text
- View/download PDF
44. Researchers from University of Gothenburg Detail New Studies and Findings in the Area of Inflammatory Bowel Disease (Mucus Layers in Inflammatory Bowel Disease)
- Subjects
Medical research ,Gastrointestinal diseases -- Research ,Health - Abstract
By a News Reporter-Staff News Editor at Gastroenterology Week -- Investigators discuss new findings in Inflammatory Bowel Disease. According to news reporting from Gothenburg, Sweden, by NewsRx editors, the research [...]
- Published
- 2014
45. Unstirred Mucus Layers: Ion Exchange Properties and Effect on Ion Regulation in Lymnaea Stagnalis
- Author
-
Schlichter, L. C.
- Abstract
Mucus from the footsole of the freshwater snail Lymnaea stagnate behaves as a weak, negatively charged ion exchanger. Activities and concentrations of Na, K, Ca, and Cl were measured in mucus dialysed to equilibrium against artificial pond water or physiological saline. Observed activity coefficients (activity/concentration) in mucus were compared with those predicted by the Debye-Huckel theory to interpret the effects of electrostatic forces between the polyelectrolyte ions and small ions. The affinity of mucus for small ions decreased in the series, Ca2+, K+, Na+, Cl−. The extent to which mucus can concentrate cations was measured using three different methods: by titrating the fixed acidic groups with K or Ca and by equilibrium dialysis after which the electrical potential difference was either measured directly or was calculated from the Nernst potential for Na. Ion exchange titration indicated a much smaller exchange capacity than did the other two methods. Kinetics of cation uptake by the snail from dilute media were re-interpreted by considering the enhanced concentrations of cations in the mucus layer. It was shown that the presence of mucus in the unstirred layer adjacent to a transporting epithelium can result in an underestimate of the Michaelis constant (Km) determined from influx measurements.
- Published
- 1982
- Full Text
- View/download PDF
46. Effects of prostaglandins on the two different gastric mucus layers in the anesthetized rat
- Author
-
M. Johansson and L. Holm
- Subjects
medicine.medical_specialty ,Endocrinology ,Hepatology ,Chemistry ,Internal medicine ,Gastric mucus ,Gastroenterology ,medicine - Published
- 1998
- Full Text
- View/download PDF
47. Bacterial populations and adaptations in the mucus layers on living corals1
- Author
-
Hugh W. Ducklow and Ralph Mitchell
- Subjects
Cnidaria ,geography ,education.field_of_study ,geography.geographical_feature_category ,food.ingredient ,biology ,Ecology ,Coral ,Heteroxenia ,fungi ,Population ,technology, industry, and agriculture ,biochemical phenomena, metabolism, and nutrition ,Aquatic Science ,Oceanography ,biology.organism_classification ,Mucus ,Porites astreoides ,food ,population characteristics ,education ,Energy source ,Reef ,geographic locations - Abstract
The external mucus layers of the stony coral Porites astreoides and the soft corals Palythoa sp. and Heteroxenia fuscesens are inhabited by communities of marine heterotrophic bacteria. Population levels of bacteria in coral mucus may be regulated by the self-cleaning behavior of the host. Bacterial populations in coral mucus respond to stresses applied to the host coral by growing to higher population levels in the mucus, indicating that these are populations of viable organisms closely attuned to host metabolism. Members of these microbial populations utilize the mucus compounds and may play a role in processing coral mucus for reef detritus feeders. One such species, Vibrio alginolyticus, grows rapidly on Heteroxenia mucus, is attracted to dissolved mucus, and possesses a mechanism to maintain itself on the coral surface.
- Published
- 1979
- Full Text
- View/download PDF
48. Unstirred Mucus Layers: Ion Exchange Properties and Effect on Ion Regulation in Lymnaea Stagnalis
- Author
-
L. C. Schlichter
- Subjects
Activity coefficient ,Chromatography ,Ion exchange ,biology ,Physiology ,Chemistry ,Inorganic chemistry ,Lymnaea stagnalis ,Aquatic Science ,biology.organism_classification ,Mucus ,Michaelis–Menten kinetics ,Ion ,symbols.namesake ,Insect Science ,symbols ,Animal Science and Zoology ,Titration ,Nernst equation ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics - Abstract
Mucus from the footsole of the freshwater snail Lymnaea stagnate behaves as a weak, negatively charged ion exchanger. Activities and concentrations of Na, K, Ca, and Cl were measured in mucus dialysed to equilibrium against artificial pond water or physiological saline. Observed activity coefficients (activity/concentration) in mucus were compared with those predicted by the Debye-Huckel theory to interpret the effects of electrostatic forces between the polyelectrolyte ions and small ions. The affinity of mucus for small ions decreased in the series, Ca2+, K+, Na+, Cl−. The extent to which mucus can concentrate cations was measured using three different methods: by titrating the fixed acidic groups with K or Ca and by equilibrium dialysis after which the electrical potential difference was either measured directly or was calculated from the Nernst potential for Na. Ion exchange titration indicated a much smaller exchange capacity than did the other two methods. Kinetics of cation uptake by the snail from dilute media were re-interpreted by considering the enhanced concentrations of cations in the mucus layer. It was shown that the presence of mucus in the unstirred layer adjacent to a transporting epithelium can result in an underestimate of the Michaelis constant (Km) determined from influx measurements.
- Published
- 1982
- Full Text
- View/download PDF
49. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria.
- Published
- 2010
- Full Text
- View/download PDF
50. Colonic epithelial cell diversity in health and inflammatory bowel disease
- Author
-
Simon J. Davis, Rajinder Singh Andev, Hashem Koohy, Agne Antanaviciute, Leyuan Bao, David Fawkner-Corbett, Christoffer Lagerholm, Kaushal Parikh, Neil Ashley, Philip Hublitz, Anna Aulicino, Nasullah Khalid Alham, Roman Fischer, Marta Jagielowicz, Alison Simmons, Joanna Lukomska, Robert D. Goldin, Hannah H. Chen, Elisabet Björklund, Errin Johnson, James Kinchen, and Benedikt M. Kessler
- Subjects
Male ,0301 basic medicine ,Transcription, Genetic ,MUCIN ,Ion Channels ,Mice ,0302 clinical medicine ,Intestinal mucosa ,RNA-SEQ ,Intestinal Mucosa ,Multidisciplinary ,Tight junction ,Stem Cells ,Hydrogen-Ion Concentration ,Cell biology ,Multidisciplinary Sciences ,medicine.anatomical_structure ,Health ,030220 oncology & carcinogenesis ,Science & Technology - Other Topics ,Goblet Cells ,Single-Cell Analysis ,Stem cell ,medicine.symptom ,STEM-CELLS ,EXPRESSION ,GENES ,TISSUES ,Colon ,General Science & Technology ,Inflammation ,MUCUS LAYERS ,Biology ,DENDRITIC CELLS ,digestive system ,Tight Junctions ,03 medical and health sciences ,WAP Four-Disulfide Core Domain Protein 2 ,RESOURCE ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,Progenitor cell ,Natriuretic Peptides ,Goblet cell ,Science & Technology ,Mucin ,Proteins ,Epithelial Cells ,Inflammatory Bowel Diseases ,Mucus ,digestive system diseases ,030104 developmental biology ,Colitis, Ulcerative ,Biomarkers - Abstract
The colonic epithelium facilitates host–microorganism interactions to control mucosal immunity, coordinate nutrient recycling and form a mucus barrier. Breakdown of the epithelial barrier underpins inflammatory bowel disease (IBD). However, the specific contributions of each epithelial-cell subtype to this process are unknown. Here we profile single colonic epithelial cells from patients with IBD and unaffected controls. We identify previously unknown cellular subtypes, including gradients of progenitor cells, colonocytes and goblet cells within intestinal crypts. At the top of the crypts, we find a previously unknown absorptive cell, expressing the proton channel OTOP2 and the satiety peptide uroguanylin, that senses pH and is dysregulated in inflammation and cancer. In IBD, we observe a positional remodelling of goblet cells that coincides with downregulation of WFDC2—an antiprotease molecule that we find to be expressed by goblet cells and that inhibits bacterial growth. In vivo, WFDC2 preserves the integrity of tight junctions between epithelial cells and prevents invasion by commensal bacteria and mucosal inflammation. We delineate markers and transcriptional states, identify a colonic epithelial cell and uncover fundamental determinants of barrier breakdown in IBD. Profiling of single epithelial cells in healthy and inflamed colons identifies specialized cellular subpopulations, including a type of goblet cell that secretes the antibacterial protein WFDC2, which preserves the integrity of the epithelial barrier layer.
- Published
- 2019
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