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David J Thornton - One of the best experts on this subject based on the ideXlab platform.
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Mucins and Mucus
Mucosal Immunology, 2015Co-Authors: Michael A. Mcguckin, David J Thornton, Jeffrey A. WhitsettAbstract:Mucosal surfaces are exposed to the external environment and pathogens and are therefore protected by a secreted layer of mucus rich in Mucin glycoproteins, which are the main components of mucus. Mucus provides physical protection and hydration, excludes pathogens, and is a reservoir for antimicrobial molecules. Underlying mucus further protection is provided by epithelial cell surface Mucins, which limit microbial adherence and regulate growth and apoptosis. Differentiation of the cells that produce Mucins, and expression of Mucins and proteins involved in Mucin biosynthesis, is regulated by innate and adaptive immunity. Experimental deficiencies in Mucins lead to infectious and inflammatory diseases, and Mucin gene polymorphisms are associated with disease. Many chronic mucosal inflammatory diseases are characterized by mucus hypersecretion driven by immune and microbial factors, which contributes to pathology and is a target for therapy. In this chapter we describe the nature of this mucosal barrier, its regulation and function, and its involvement in human disease, with particular emphasis on the Mucin component of the barrier.
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particle tracking microrheology of purified gastrointestinal Mucins
Biopolymers, 2014Co-Authors: Pantelis Georgiades, David J Thornton, Paul D A Pudney, Thomas A WaighAbstract:The rheological characteristics of gastric and duodenal Mucin solutions, the building blocks of the mucus layer that covers the epithelia of the two organs, were investigated using particle tracking microrheology. We used biochemically well characterized purified porcine Mucins (MUC5AC and MUC2) as models for human Mucins, to probe their viscoelasticity as a function of Mucin concentration and pH. Furthermore, we used both reducing (dithiothreitol, DTT) and chaotropic agents (guanidinium chloride and urea) to probe the mesoscopic forces that mediate the integrity of the polymer network. At neutral pH both gastric and duodenal Mucins formed self-assembled semi-dilute networks above a certain critical Mucin concentration (c*) with the viscosity (?) scaling as ??c0.53�0.08 for MUC5AC and ??c0.53�0.06 for MUC2, where c is the Mucin concentration. Above an even higher Mucin concentration threshold (ce , the entanglement concentration) reptation occurs and there is a dramatic increase in the viscosity scaling, ??c3.92�0.38 for MUC5AC and ??c5.1�0.8 for MUC2. The dynamics of the self-assembled comb polymers is examined in terms of a scaling model for flexible polyelectrolyte combs. Both duodenum and gastric Mucin are found to be pH switchable gels, gelation occurring at low pHs. There is a hundred-fold increase in the elastic shear modulus once the pH is decreased. The addition of DTT, guanidinium chloride and urea disassembles both the semi-dilute and gel structures causing a large increase in the compliance (decrease in their shear moduli). Addition of the polyphenol EGCG has a reverse effect on Mucin viscoelasticity, that is, it triggers a sol-gel transition in semi-dilute Mucin solutions at neutral pH. � 2013 Wiley Periodicals, Inc. Biopolymers 101: 366-377, 2014.
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The expression of Mucin genes and the presence of Mucin gene products in the equine endometrium.
Research in veterinary science, 2013Co-Authors: Eva Maischberger, David J Thornton, Karine Rousseau, Carolyn A. Cummins, E. Fitzpatrick, Mary Gallagher, Sheila Worrall, Wim G. Meijer, Raúl Miranda-casoluengo, Vivienne DugganAbstract:In the equine reproductive tract, little is known about Mucin gene expression and the role of Mucins in barrier function and host-cell interaction. The aims of the study were to identify equine orthologs of mammalian Mucin genes using available equine sequence data, to profile expression of equine orthologous Mucin genes in the endometrium using reverse transcriptase polymerase chain reaction (RT-PCR), to determine spatial expression patterns of Mucin genes using in situ hybridisation, and to confirm the presence of Mucin gene products using Western blotting and equine-specific Mucin antibodies during oestrus and dioestrus. While the Mucin gene expression pattern in equine endometrium is similar to that of other mammals, several Mucins appear to be uniquely expressed in this tissue (eqMUC3B, 7, 18, and 20) and one is hormonally regulated (eqMUC3B).
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Mucins : methods and protocols
Methods in Molecular Biology, 2012Co-Authors: Michael A. Mcguckin, David J ThorntonAbstract:1. Mucin Methods: Genes Encoding Mucins And Their Genetic Variation With A Focus On Gel Forming Mucins Karine Rousseau and Dallas M. Swallow 2. Gel-forming and Cell-associated Mucins - preparation for Structural and Functional Studies Julia R. Davies, Claes Wickstrom and David J. Thornton 3. Detecting, Visualising and Quantifying Mucins Ceri A. Harrop, David J. Thornton and Michael A. McGuckin 4. Mass Spectrometric Analysis of Mucin Core Proteins Mehmet Kesimer and John K. Sheehan 5. O-Glycoprotein Biosynthesis: Site Localization by Edman Degradation and Site Prediction Based on Random Peptide Substrates Thomas A. Gerken 6. Analysis of Assembly of Secreted Mucins Malin E.V. Johansson and Gunnar C. Hansson 7. MUC1 Membrane Trafficking: Protocols for Assessing Biosynthetic Delivery, Endocytosis, Recycling and Release Through Exosomes Franz-Georg Hanisch, Carol L. Kinlough, Simon Staubach, Rebecca P. Hughey 8.Glycomic Work-flow for Analysis of Mucin O-linked Oligosaccharides Catherine A. Hayes, Szilard Nemes, Samah Issa, Chunseng Jin, and Niclas G. Karlsson 9. O-Glycomics: Profoliling and Structural Analysis of Mucin-type O-linked Glycans Isabelle Breloy 10. O-Glycoproteomics: Site-specific O-glycoprotein Analysis by CID/ETD Electrospray Ionization Tandem Mass Spectrometry and Top-Down Glycoprotein Sequencing by In-Source Decay MALDI Mass Spectrometry Franz-Georg Hanisch 11. Analysing Mucin Degradation Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield Stephen D. Carrington, Jane A. Irwin, Li Liu, Pauline Rudd, Elizabeth Matthews, and Anthony P. Corfield 12. Assessment of Mucus Thickness and Production In Situ Lena Holm and Mia Phillipson 13. Preservation of Mucus in Histrological Sections, Immunostaining of Mucins in Fixed Tissue and Localization of Bacteria with FISH Malin E.V. Johansson and Gunnar C. Hansson 14. In vitro Measurements of Mucus Secretion by Colon Explants Jenny K. Gustafsson, Henrik Sjovall and Gunnar C. Hansson 15. Establishment of Respiratory Air-Liquid Interface Cultures and their Use in Studying Mucin Production, Secretion, and Function David R. Hill and Brian Button David R. Hill and Brian Button David R. Hill and Brian Button David R. Hill and Brian Button 16. Studying Mucin Secretion from Human Bronchial Epithelial Cell Primary Cultures Lubna H. Abdullah, Cedric Wolber, Mehment Kesimer, John K. Sheehan, and C. William Davis 17. Assessment of Intracellular Mucin Content In Vivo Lucia Piccotti, Burton F. Dickey, Christopher M. Evans 18. Techniques for Assessment of Interactions of Mucins with Microbes and Parasites In Vitro and In Vivo Yong H. Sheng, Sumaira Z. Hasain, Chin Wen Png, Michael A. McGuckin and Sara K. Linden 19. Assessing Mucin Expression and Function in Human Ocular Surface Epithelia In Vivo and In Vitro Pablo Augueso and Ilene K. Gipson 16. Studying Mucin Secretion from Human Bronchial Epithelial Cell Primary Cultures Lubna H. Abdullah, Cedric Wolber, Mehment Kesimer, John K. Sheehan, and C. William Davis 17. Assessment of Intracellular Mucin Content In Vivo Lucia Piccotti, Burton F. Dickey, Christopher M. Evans 18. Techniques for Assessment of Interactions of Mucins with Microbes and Parasites In Vitro and In Vivo Yong H. Sheng, Sumaira Z. Hasain, Chin Wen Png, Michael A. McGuckin and Sara K. Linden 19. Assessing Mucin Expression and Function in Human Ocular Surface Epithelia In Vivo and In Vitro Pablo Augueso and Ilene K. Gipson
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Detecting, visualising, and quantifying Mucins.
Methods in molecular biology (Clifton N.J.), 2011Co-Authors: Ceri A. Harrop, David J Thornton, Michael A. McguckinAbstract:The extreme size, extensive glycosylation, and gel-forming nature of Mucins make them a challenge to work with, and methodologies for the detection of Mucins must take into consideration these features to ensure that one obtains both accurate and meaningful results. In understanding and appreciating the nature of Mucins, this affords the researcher a valuable toolkit which can be used to full advantage in detecting, quantifying, and visualising Mucins. The employment of a combinatorial approach to Mucin detection, using antibody, chemical, and lectin detection methods, allows important information to be gleaned regarding the size, extent of glycosylation, specific Mucin species, and distribution of Mucins within a given sample. In this chapter, the researcher is guided through considerations into the structure of Mucins and how this both affects the detection of Mucins and can be used to full advantage. Techniques including ELISA, dot/slot blotting, and Western blotting, use of lectins and antibodies in Mucin detection on membranes as well as immunohistochemistry and immunofluorescence on both tissues and cells grown on Transwell? inserts are described. Notes along with each section advice the researcher on best practice and describe any associated limitations of a particular technique from which the researcher can further develop a particular protocol.
Sara K. Lindén - One of the best experts on this subject based on the ideXlab platform.
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Role of Sialic Acid in Brachyspira hyodysenteriae Adhesion to Pig Colonic Mucins.
Infection and immunity, 2019Co-Authors: Macarena P. Quintana-hayashi, Freddy Haesebrouck, Vignesh Venkatakrishnan, Sara K. LindénAbstract:Infection with Brachyspira hyodysenteriae results in mucoid hemorrhagic diarrhea. This pathogen is associated with the colonic mucus layer, mainly composed of Mucins. Infection regulates Mucin O-glycosylation in the colon and increases Mucin secretion as well as B. hyodysenteriae binding sites on Mucins. Here, we analyzed potential Mucin epitopes for B. hyodysenteriae adhesion in the colon, as well as the effect of colonic Mucins on bacterial growth. Associations between B. hyodysenteriae binding to pig colonic Mucins and Mucin glycan data showed that B. hyodysenteriae binding was associated with the presence of N-glycolylneuraminic acid (NeuGc) on Mucins. The role of sialic acid in B. hyodysenteriae adhesion was analyzed after the removal of sialic acid residues on the Mucins by enzymatic treatment with sialidase A, which decreased bacterial binding to the Mucins. The effect of pig colonic Mucins on B. hyodysenteriae growth was determined in carbohydrate-free medium. B. hyodysenteriae growth increased in the presence of Mucins from two out of five infected pigs, suggesting utilization of Mucins as a carbon source for growth. Additionally, bacterial growth was enhanced by free sialic acid and N-acetylglucosamine. The results highlight a role of sialic acid as an adhesion epitope for B. hyodysenteriae interaction with colonic Mucins. Furthermore, the Mucin response and glycosylation changes exerted in the colon during B. hyodysenteriae infection result in a potentially favorable environment for pathogen growth in the intestinal mucus layer.
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aeromonas salmonicida binds differentially to Mucins isolated from skin and intestinal regions of atlantic salmon in an n acetylneuraminic acid dependent manner
Infection and Immunity, 2014Co-Authors: János Tamás Padra, Niclas G. Karlsson, Henrik Sundh, Kristina Sundell, Chunsheng Jin, Sara K. LindénAbstract:Aeromonas salmonicida subsp. salmonicida infection, also known as furunculosis disease, is associated with high morbidity and mortality in salmonid aquaculture. The first line of defense the pathogen encounters is the mucus layer, which is predominantly comprised of secreted Mucins. Here we isolated and characterized Mucins from the skin and intestinal tract of healthy Atlantic salmon and studied how A. salmonicida bound to them. The Mucins from the skin, pyloric ceca, and proximal and distal intestine mainly consisted of Mucins soluble in chaotropic agents. The Mucin density and Mucin glycan chain length from the skin were lower than were seen with Mucin from the intestinal tract. A. salmonicida bound to the Mucins isolated from the intestinal tract to a greater extent than to the skin Mucins. The Mucins from the intestinal regions had higher levels of sialylation than the skin Mucins. Desialylating intestinal Mucins decreased A. salmonicida binding, whereas desialylation of skin Mucins resulted in complete loss of binding. In line with this, A. salmonicida also bound better to mammalian Mucins with high levels of sialylation, and N-acetylneuraminic acid appeared to be the sialic acid whose presence was imperative for binding. Thus, sialylated structures are important for A. salmonicida binding, suggesting a pivotal role for sialylation in mucosal defense. The marked differences in sialylation as well as A. salmonicida binding between the skin and intestinal tract suggest interorgan differences in the host-pathogen interaction and in the Mucin defense against A. salmonicida.
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human gastric Mucins differently regulate helicobacter pylori proliferation gene expression and interactions with host cells
PLOS ONE, 2012Co-Authors: Emma C Skoog, Jan Holgersson, Asa Sjoling, Nazanin Navabi, Samuel Lundin, Sara K. LindénAbstract:Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated Mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified Mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that Mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The Mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of Mucins and the ability of the Mucins to bind to H. pylori. Tumor-derived Mucins and Mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived Mucins tended to inhibit proliferation and Mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human Mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA) appeared co-regulated in response to Mucins. The addition of Mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other Mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric Mucin environment, demonstrating a dynamic interplay between the bacterium and its host.
Vijay R. Ramakrishnan - One of the best experts on this subject based on the ideXlab platform.
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Differential Expression of Mucins in Murine Olfactory Versus Respiratory Epithelium
Chemical senses, 2019Co-Authors: Christopher Kennel, Elizabeth A. Gould, Eric D. Larson, Ernesto Salcedo, Thad W. Vickery, Diego Restrepo, Vijay R. RamakrishnanAbstract:Mucins are a key component of the surface mucus overlying airway epithelium. Given the different functions of the olfactory and respiratory epithelia, we hypothesized that Mucins would be differentially expressed between these 2 areas. Secondarily, we evaluated for potential changes in Mucin expression with radiation exposure, given the clinical observations of nasal dryness, altered mucus rheology, and smell loss in radiated patients. Immunofluorescence staining was performed to evaluate expression of Mucins 1, 2, 5AC, and 5B in nasal respiratory and olfactory epithelia of control mice and 1 week after exposure to 8 Gy of radiation. Mucins 1, 5AC, and 5B exhibited differential expression patterns between olfactory and respiratory epithelium (RE) while Mucin 2 showed no difference. In the olfactory epithelium (OE), Mucin 1 was located in a lattice-like pattern around gaps corresponding to dendritic knobs of olfactory sensory neurons, whereas in RE it was intermittently expressed by surface goblet cells. Mucin 5AC was expressed by subepithelial glands in both epithelial types but to a higher degree in the OE. Mucin 5B was expressed by submucosal glands in OE and by surface epithelial cells in RE. At 1-week after exposure to single-dose 8 Gy of radiation, no qualitative effects were seen on Mucin expression. Our findings demonstrate that murine OE and RE express Mucins differently, and characteristic patterns of Mucins 1, 5AC, and 5B can be used to define the underlying epithelium. Radiation (8 Gy) does not appear to affect Mucin expression at 1 week. N/A (Basic Science Research).IACUC-approved study [Protocol 200065]. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Differential Expression of Mucins in Murine Olfactory Versus Respiratory Epithelium
2019Co-Authors: Christopher Kennel, Elizabeth A. Gould, Eric D. Larson, Ernesto Salcedo, Thad W. Vickery, Diego Restrepo, Vijay R. RamakrishnanAbstract:Abstract Mucins are a key component of the airway surface liquid and serve many functions. Given the numerous differences in olfactory versus respiratory nasal epithelia, we hypothesized that Mucins would be differentially expressed between these two areas. Secondarily, we evaluated for changes in Mucin expression with radiation exposure, given the clinical observations of nasal dryness, altered mucus rheology, and smell loss in radiated patients. Immunofluorescence staining was performed in a mouse model to determine the expression of Mucins 1, 2, 5AC and 5B in nasal respiratory and olfactory epithelia of control mice and one week after exposure to 8 gy of radiation. Mucins 1, 5AC and 5B exhibited differential expression between olfactory and respiratory epithelium while Mucin 2 showed no difference. Within the olfactory epithelium, Mucin 1 was located in a lattice-like pattern around gaps corresponding to dendritic knobs of olfactory sensory neurons, whereas in respiratory epithelium it was only intermittently expressed. Mucin 5AC was expressed by subepithelial glands in both epithelial types but to a higher degree in the olfactory epithelium. Mucin 5B was expressed by submucosal glands in the olfactory epithelium but by surface epithelial cells in respiratory epithelium. At one-week after exposure to single-dose 8 gy of radiation, no qualitative effects were seen on Mucin expression. Our findings demonstrate that murine olfactory and respiratory epithelia express Mucins differently, and characteristic patterns of Mucins 1, 5AC, and 5B can be used to define the underlying epithelium. Radiation (8 gy) does not appear to affect Mucin expression at one week. Author Roles Christopher Kennel conceived, organized and executed the study, performed the analysis, and contributed to the manuscript. Elizabeth Gould conceived and executed the study, and contributed to the manuscript. Diego Restrepo conceived and executed the study, supervised the experiments, reviewed the analysis, and contributed to the manuscript. Ernesto Salcedo performed experiments and reviewed the manuscript. Thad Vickery performed experiments and reviewed the manuscript. Eric Larson performed experiments and reviewed the manuscript. Vijay Ramakrishnan conceived and executed the study, reviewed the analysis, and contributed to the manuscript. All authors discussed the results and implications and contributed to the final manuscript.
Ilene K Gipson - One of the best experts on this subject based on the ideXlab platform.
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Mucins and contact lens wear.
Cornea, 2006Co-Authors: Yuichi Hori, Pablo Argueso, Sandra Spurr-michaud, Ilene K GipsonAbstract:PURPOSE This study was designed to determine whether long-term tolerant contact lens (CL) wear causes changes in the expression of Mucin mRNA by the conjunctival epithelium and Mucin protein content in tears and to determine whether specific Mucins adhere to contact lenses. METHODS Twenty long-term (> or = 5 years ) and tolerant CL wearers (2 with hard and 18 with soft contact lenses) were compared with 23 non-CL wearers. One hour after CL removal, tear fluid was collected after instillation of 60 microL of sterile water onto the ocular surface, and protein concentration was determined. Impression cytology was performed on the bulbar temporal region of conjunctiva to collect cells for RNA isolation. Real-time polymerase chain reaction was performed using TaqMan primer and probes for MUC1, 4, 5AC, and 16. ELISA was performed on the collected tears to detect MUC5AC and the Mucin carbohydrate epitope H185. For the analysis of adherent Mucins on CL, discarded daily-wear contact lenses were collected, rinsed, and incubated overnight at 4 degrees C in Mucin isolation buffer. Immunoblot analysis of adherent Mucins was performed to detect MUC1, 4, 5AC, 16, and H185. RESULTS No significant changes in the levels of Mucin mRNA from impression cytology samples were detected when comparing CL and non-CL wearers. The amount of total protein in tears collected from CL wearers (39.9 +/- 27.2 microg) was significantly less than that from non-CL wearers (95.1 +/- 73.8 microg, P = 0.001). The level of MUC5AC Mucin and the H185 epitope in tears per unit protein in CL wearers was not significantly different from non-CL wearers. Low levels of membrane-associated Mucins, the secreted Mucin MUC5AC, and the carbohydrate epitope, H185, were detected in protein extracts from discarded CLs. Compared with MUC1, 4, and 5AC, there was less MUC16 adherent to the CLs. CONCLUSION Neither Mucin mRNA expression by conjunctival epithelia nor Mucin content per unit protein in tears was altered by long-term tolerant CL wear; however, the amount of protein in the tears was significantly less. Shed membrane-associated Mucins and the goblet cell Mucins adhere to CLs.
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character of ocular surface Mucins and their alteration in dry eye disease
Ocular Surface, 2004Co-Authors: Ilene K Gipson, Yuichi Hori, Pablo ArguesoAbstract:At the ocular surface, three types of Mucins are present. The large gel-forming Mucin MUC5AC is expressed by conjunctival goblet cells. Some cells of the lacrimal gland acini express the small soluble Mucin MUC7. The corneal and conjunctival epithelia express the membrane-associated Mucins MUCs 1, 4, and 16. With the characterization of the Mucin gene repertoire of the ocular surface epithelia, studies of the function of specific Mucins, their gene regulation, and their alteration in ocular surface disease have begun. Current information suggests that all the Mucins are hydrophilic and play a role in maintenance of water on the surface of the eye. The large secreted Mucins represent the "janitorial service" that moves over the surface of the eye to wrap up and remove debris. The membrane-associated Mucins form the glycocalyx, which provides a continuous barrier across the surface of the eye that prevents pathogen penetrance and has signaling capabilities that influence epithelial activity. Factors regulating Mucin gene expression include retinoic acid, serum, and dexamethasone. Alteration in both secreted and membrane-associated Mucins occur in drying ocular surface diseases. In Sjogren syndrome, MUC5AC expression is reduced, and in non-Sjogren dry eye, glycosylation of MUC16 appears to be altered. The pattern of expression of enzymes that glycosylate Mucins is altered in ocular cicatricial pemphigoid. Therapies being evaluated for dry eye, including cyclosporine A, P2Y2 agonists, gefarnate, 15-(S)-HETE, and corticosteroids, may be efficacious due to their effect on Mucin gene expression and secretion.
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Distribution of Mucins at the ocular surface
Experimental eye research, 2004Co-Authors: Ilene K GipsonAbstract:Mucins are vital for maintenance of a healthy, wet ocular surface. Once only thought to be secreted by goblet cells, Mucins are now also known to be of the membrane-associated type. Stratified ocular surface epithelia express at their apical-tear fluid surface a repertoire of membrane-associated Mucins including MUC1, MUC4, MUC16. These Mucins are concentrated on the tips of the microplicae, forming a dense glycocalyx at the epithelial tear film interface. A major Mucin of the secretory class is the goblet-cell-derived gel-forming Mucin MUC5AC. A small soluble Mucin, MUC7, is expressed by the lacrimal gland acini. Our hypothesis of the role/distribution of the secreted and membrane-associated Mucins at the ocular surface is that the secreted Mucins are soluble in the tear fluid, and are moved about and shunted to the nasolacrimal duct and by the eyelids during blinking. Thus, in the tears, the secreted Mucins act as clean-up/debris removing multimeric networks that at the same time, through their hydrophilic nature, hold fluids in place and harbor defense molecules secreted by the lacrimal gland. Membrane-associated Mucins, on the other hand, form a dense barrier in the glycocalyx at the epithelial tear film interface. This barrier prevents pathogen penetrance and is a lubricating surface that allows lid epithelia to glide over the corneal epithelia without adherence. The secreted Mucins move easily over the glycocalyx Mucins because both have anionic character that creates repulsive forces between them. Little is known regarding regulation of expression and glycosylation of Mucins by ocular surface epithelia. Since ocular surface drying diseases alter both goblet cell and Mucin production, and production and glycosylation of membrane-associated Mucins, studies of Mucin gene regulation and glycosylation may yield treatment modalities for these diseases.
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role of Mucins in the function of the corneal and conjunctival epithelia
International Review of Cytology-a Survey of Cell Biology, 2003Co-Authors: Ilene K Gipson, Pablo ArguesoAbstract:The surface of the eye is covered by a tear film, which is held in place by a wet-surfaced, stratified, corneal and conjunctival epithelia. Both are vital for light refraction and protection of vision. Maintenance of tear film on the ocular surface, lubrication, and provision of a pathogen barrier on this wet surface is facilitated by a class of large, highly glycosylated, hydrophilic glycoproteins--the Mucins. In the past 15 years, a number of Mucin genes have been cloned, and based on protein sequence, categorized as either secreted or membrane associated. Both types of Mucins are expressed by ocular surface epithelia. Goblet cells intercalated within the stratified epithelium of the conjunctiva secrete the large gel-forming Mucin MUC5AC, and lacrimal gland epithelia secrete the small soluble Mucin MUC7. Apical cells of the stratified epithelium of both corneal and conjunctival epithelium express at least three membrane-associated Mucins (MUCs 1, 4, and 16), which extend from their apical surface to form the thick glycocalyx at the epithelium-tear film interface. The current hypothesis regarding Mucin function and tear film structure is that the secreted Mucins form a hydrophilic blanket that moves over the glycocalyx of the ocular surface to clear debris and pathogens. Mucins of the glycocalyx prevent cell-cell and cell-pathogen adherence. The expression and glycosylation of Mucins are altered in drying, keratinizing ocular surface diseases.
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Mucins of the human endocervix.
Frontiers in bioscience : a journal and virtual library, 2001Co-Authors: Ilene K GipsonAbstract:The physical character and amount of mucus secreted by the endocervix changes dramatically at midcycle to facilitate the reproductive process. Mucins expressed by the endocervical epithelium contribute to this all-important physiologic event. This review summarizes work from our laboratory demonstrating the Mucin gene expression profile of cervical epithelium and Mucin levels in cervical mucus through the menstrual cycle. mRNA levels of the gel-forming Mucin MUC5B, the major gel-forming Mucin expressed by the endocervical epithelium, peak before midcycle and the amount of MUC5B protein per unit total protein in cervical mucus peaks at midcycle. Message levels for MUC4, a major membrane-spanning Mucin of the endocervix, peak at midcycle, but protein levels of MUC4 in human cervical mucus have not been measured. Message for each Mucin diminishes dramatically as progesterone levels increase in the blood. These data suggest hormonal regulation of the two Mucin genes in the endocervix, but there is no information on their regulation at the biosynthetic level via genomic hormone response elements. Perhaps, through its hydrophilicity, the MUC5B Mucin holds water in place at the endocervical canal surface at midcycle, keeping the canal patent for sperm motility. A second potential role of the increased Mucins at midcycle is to protect the cervix and uterus at the time when increased water is secreted into the cervical canal to facilitate sperm penetrance. Pathogens and other seminal fluid components may be excluded from entering the uterus by Mucin trapping. Studies to determine the mechanism of hormonal regulation of Mucins as well as the function of individual Mucins are needed.
Judith A. Voynow - One of the best experts on this subject based on the ideXlab platform.
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Mucins, Mucus, and Goblet Cells
Chest, 2017Co-Authors: Bruce K. Rubin, Judith A. VoynowAbstract:The respiratory epithelium is lined by mucus, a gel consisting of water, ions, proteins, and macromolecules. The major macromolecular components of mucus are the Mucin glycoproteins, which are critical for local defense of the airway. There are three classes of Mucins in the airways: those that are secreted but do not polymerize (MUC7), those that are secreted and polymerize to form gels (MUC5AC, MUC5B), and those that have transmembrane domains and are cell surface associated (MUC1, MUC4, MUC16, MUC20). The Mucins are regulated at the transcriptional, posttranscriptional, and epigenetic levels, and posttranslational modifications play an important role in Mucin binding and clearance of microbes and pollutants. The development of mice deficient in specific Mucins, and the cystic fibrosis pig, has greatly advanced our understanding of the role of Mucins as innate immune mediators and how Mucins and mucus contribute to lung disease. These observations suggest new strategies to ameliorate mucus obstruction by targeting mucociliary clearance and Mucin hyperconcentration. Furthermore, a polymorphism in the promoter of MUC5B is strongly associated with risk of developing pulmonary fibrosis, supporting a novel function for MUC5B to influence interstitial lung disease. Exciting new data support the concept not only that Mucins and mucus are important for lung homeostasis and protection from environmental threats but also that goblet cells play an important role as regulators of innate immune function. These insights into the innate immune properties of Mucins and goblet cells support a shift from the current paradigm of repressing increased Mucin expression to targeting regulation of specific Mucins and the abnormal airway milieu.
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Mucins, Mucus, and Sputum*
Chest, 2009Co-Authors: Judith A. Voynow, Bruce K. RubinAbstract:Normal airway mucus lines the epithelial surface and provides an important innate immune function by detoxifying noxious molecules and by trapping and removing pathogens and particulates from the airway via mucociliary clearance. The major macromolecular constituents of normal mucus, the Mucin glycoproteins, are large, heavily glycosylated proteins with a defining feature of tandemly repeating sequences of amino acids rich in serine and threonine, the linkage sites for large carbohydrate structures. The Mucins are composed of two major families: secreted Mucins and membrane-associated Mucins. Membrane-associated Mucins have been reported to function as cell surface receptors for pathogens and to activate intracellular signaling pathways. The biochemical and cellular functions for secreted Mucin glycoproteins have not been definitively assigned. In contrast to normal mucus, sputum production is the hallmark of chronic inflammatory airway diseases such as asthma, chronic bronchitis, and cystic fibrosis (CF). Sputum has altered macromolecular composition and biophysical properties which vary with disease, but unifying features are failure of mucociliary clearance, resulting in airway obstruction, and failure of innate immune properties. Mucin glycoprotein overproduction and hypersecretion are common features of chronic inflammatory airway disease, and this has been the underlying rationale to investigate the mechanisms of Mucin gene regulation and Mucin secretion. However, in some pathologic conditions such as CF, airway sputum contains little intact Mucin and has increased content of several macromolecules including DNA, filamentous actin, lipids, and proteoglycans. This review will highlight the most recent insights on mucus biology in health and disease.
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Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease
Physiological reviews, 2006Co-Authors: Mary C. Rose, Judith A. VoynowAbstract:This review focuses on the role and regulation of Mucin glycoproteins (Mucins) in airway health and disease. Mucins are highly glycosylated macromolecules (≥50% carbohydrate, wt/wt). MUC protein ba...
