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Frontiers in Immunology 2023The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. The major components of mucus...
The colonic mucus bilayer is the first line of innate host defense that at the same time houses and nourishes the commensal microbiota. The major components of mucus secreted by goblet cells are MUC2 mucin and the mucus-associated protein, FCGBP (IgGFc-binding protein). In this study, we determine if FCGBP and MUC2 mucin were biosynthesized and interacted together to spatially enhance the structural integrity of secreted mucus and its role in epithelial barrier function. MUC2 and FCGBP were coordinately regulated temporally in goblet-like cells and in response to a mucus secretagogue but not in CRISPR-Cas9 gene-edited cells. Whereas ~85% of MUC2 was colocalized with FCGBP in mucin granules, ~50% of FCGBP was diffusely distributed in the cytoplasm of goblet-like cells. STRING-db v11 analysis of the mucin granule proteome revealed no protein-protein interaction between MUC2 and FCGBP. However, FCGBP interacted with other mucus-associated proteins. FCGBP and MUC2 interacted via N-linked glycans and were non-covalently bound in secreted mucus with cleaved low molecular weight FCGBP fragments. In , cytoplasmic FCGBP was significantly increased and diffusely distributed in wounded cells that healed by enhanced proliferation and migration within 2 days, whereas, in WT cells, MUC2 and FCGBP were highly polarized at the wound margin which impeded wound closure by 6 days. In DSS colitis, restitution and healed lesions in but not littermates, were accompanied by a rapid increase in mRNA and delayed protein expression at 12- and 15-days post DSS, implicating a potential novel endogenous protective role for FCGBP in wound healing to maintain epithelial barrier function.
Topics: Colitis; Goblet Cells; Mucins; Wound Healing; Animals; Mice
PubMed: 37359538
DOI: 10.3389/fimmu.2023.1211336 -
Glycobiology Jun 2021The gut microbiota plays a major role in human health and an alteration in gut microbiota structure and function has been implicated in several diseases. In the colon,... (Review)
Review
The gut microbiota plays a major role in human health and an alteration in gut microbiota structure and function has been implicated in several diseases. In the colon, mucus covering the epithelium is critical to maintain a homeostatic relationship with the gut microbiota by harboring a microbial community at safe distance from the epithelium surface. The mucin glycans composing the mucus layer provide binding sites and a sustainable source of nutrients to the bacteria inhabiting the mucus niche. Access to these glycan chains requires a complement of glycoside hydrolases (GHs) produced by bacteria across the phyla constituting the human gut microbiota. Due to the increased recognition of the role of mucus-associated microbes in human health, how commensal bacteria breakdown and utilize host mucin glycans has become of increased interest and is reviewed here. This short review provides an overview of the strategies evolved by gut commensal bacteria to access this rich source of the nutrient with a focus on the GHs involved in mucin degradation.
Topics: Colon; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mucins; Polysaccharides
PubMed: 33043970
DOI: 10.1093/glycob/cwaa097 -
Respiratory Research Nov 2019Mucus secretion and mucociliary transport are essential defense mechanisms of the airways. Deviations in mucus composition and secretion can impede mucociliary transport... (Review)
Review
Mucus secretion and mucociliary transport are essential defense mechanisms of the airways. Deviations in mucus composition and secretion can impede mucociliary transport and elicit airway obstruction. As such, mucus abnormalities are hallmark features of many respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Studying mucus composition and its physical properties has therefore been of significant interest both clinically and scientifically. Yet, measuring mucus production, output, composition and transport presents several challenges. Here we summarize and discuss the advantages and limitations of several techniques from five broadly characterized strategies used to measure mucus secretion, composition and mucociliary transport, with an emphasis on the gel-forming mucins. Further, we summarize advances in the field, as well as suggest potential areas of improvement moving forward.
Topics: Animals; Bronchoscopy; Humans; Mucins; Mucociliary Clearance; Mucus; Respiration Disorders
PubMed: 31752894
DOI: 10.1186/s12931-019-1239-z -
PeerJ 2022Mucins are part of the glycoprotein family and the main proteinaceous component of mucus. The sea anemone species, (Phylum Cnidaria) produce large amounts of mucus,...
BACKGROUND
Mucins are part of the glycoprotein family and the main proteinaceous component of mucus. The sea anemone species, (Phylum Cnidaria) produce large amounts of mucus, which have not been studied in detail. Furthermore, there has only been limited investigation of mucin genes in phylum Cnidaria. Therefore, the aim of current study was to identify and analyse the repertoire mucin genes present in and range of other sea anemone species to document their diversity in this group.
METHODS
To achieve this aim, we undertook transcriptome sequencing, assembly, and annotation to identify mucin genes in .
RESULTS
The results from this study demonstrated a diverse repertoire of mucin proteins, including mucin1-like, mucin4-like, and a range of mucin-like genes in the range of sea anemone species examined. The domain structure of the identified mucin genes was found to be consistent with the conserved domains found in the homologous proteins of vertebrate species. The discovery of a diverse range of mucin genes in sea anemone species provided a basic reference for future mucin studies in cnidarians and could lead to research into their application in the pharmacological, clinical, and cosmetic industries.
Topics: Animals; Sea Anemones; Mucins; Proteins; Vertebrates
PubMed: 35539013
DOI: 10.7717/peerj.13292 -
Frontiers in Cellular and Infection... 2022The mucosal surfaces that form the boundary between the external environment and the underlying tissue are protected by a mucus barrier. Mucin glycoproteins, both... (Review)
Review
The mucosal surfaces that form the boundary between the external environment and the underlying tissue are protected by a mucus barrier. Mucin glycoproteins, both secreted and cell surface mucins, are the major components of the barrier. They can exclude pathogens and toxins while hosting the commensal bacteria. In this review, we highlight the dynamic function of the mucins and mucus during infection, how this mucosal barrier is regulated, and how pathogens have evolved mechanisms to evade this defence system.
Topics: Bacteria; Glycoproteins; Mucins; Mucous Membrane; Mucus
PubMed: 35774401
DOI: 10.3389/fcimb.2022.856962 -
Cancer Medicine Sep 2023Better predictors of patients with stage II/III gastric cancer (GC) most likely to benefit from adjuvant chemotherapy are urgently needed. This study aimed to assess the...
BACKGROUND
Better predictors of patients with stage II/III gastric cancer (GC) most likely to benefit from adjuvant chemotherapy are urgently needed. This study aimed to assess the ability of CDX2 and mucin markers to predict prognosis and fluorouracil-based adjuvant chemotherapy benefits.
METHODS
CDX2 and mucin protein expressions were examined by immunohistochemistry and compared with survival and adjuvant chemotherapy benefits in a prospective evaluation cohort of 782 stage II/III GC patients. Then, the main findings were validated in an independent validation cohort (n = 386) and an external mRNA sequencing dataset (ACRG cohort, n = 193).
RESULTS
In the evaluation cohort, CDX2, CD10, MUC2, MUC5AC, and MUC6 expressions were observed in 59.7%, 26.7%, 27.6%, 55.1%, and 57.7% of patients, respectively. However, only the expression of CDX2 was found to be associated with adjuvant chemotherapy benefits. Most importantly, CDX2-negative patients had a poorer prognosis when treated with surgery only, while the prognosis of CDX2-negative and CDX2-positive patients was similar when receiving postoperative adjuvant chemotherapy. Further analysis revealed that patients with CDX2 negative tumors benefited from chemotherapy (5-year overall survival rates: 60.0% with chemotherapy vs. 23.2% with surgery-only, p < 0.001), whereas patients with CDX2 positive tumors did not (p = 0.004). Consistent results were obtained in the validation and ACRG cohorts.
CONCLUSIONS
Negative expression of CDX2 is an independent risk factor for survival in stage II/III GC, but subsequent adjuvant chemotherapy is able to compensate for this unfavorable effect. Therefore, active chemotherapy is more urgent for patients with negative CDX2 expression than for patients with positive CDX2 expression.
Topics: Humans; Mucins; Stomach Neoplasms; CDX2 Transcription Factor; Biomarkers, Tumor; Prognosis; Chemotherapy, Adjuvant
PubMed: 37602699
DOI: 10.1002/cam4.6379 -
G3 (Bethesda, Md.) Jul 2022Epithelia exposed to elements of the environment are protected by a mucus barrier in mammals. This barrier also serves to lubricate during organ movements and to mediate...
Epithelia exposed to elements of the environment are protected by a mucus barrier in mammals. This barrier also serves to lubricate during organ movements and to mediate substance exchanges between the environmental milieu and internal organs. A major component of the mucus barrier is a class of glycosylated proteins called Mucin. Mucin and mucin-related proteins are widely present in the animal kingdom. Mucin mis-regulation has been reported in many diseases such as cancers and ones involving the digestive and respiratory tracts. Although the biophysical properties of isolated Mucins have been extensively studied, in vivo models remain scarce for the study of their functions and regulations. Here, we characterize the Mucin-like JiangShi protein and its mutations in the fruit fly Drosophila. JiangShi is an extracellular glycoprotein with domain features reminiscent of mammalian nonmembranous Mucins, and one of the most widely distributed Mucin-like proteins studied in Drosophila. Both loss and over-production of JiangShi lead to terminal defects in adult structures and organismal death. Although the physiological function of JiangShi remains poorly defined, we present a genetically tractable model system for the in vivo studies of Mucin-like molecules.
Topics: Animals; Drosophila; Glycoproteins; Glycosylation; Mammals; Mucins; Respiratory System
PubMed: 35595239
DOI: 10.1093/g3journal/jkac126 -
Nature Communications Dec 2022Methods capable of manipulating bacterial colonization are of great significance for modulating host-microbiota relationships. Here, we describe a strategy of in-situ...
Methods capable of manipulating bacterial colonization are of great significance for modulating host-microbiota relationships. Here, we describe a strategy of in-situ chemical reaction-mediated covalent localization of bacteria. Through a simple one-step imidoester reaction, primary amino groups on bacterial surface can be converted to free thiols under cytocompatible conditions. Surface thiolation is applicable to modify diverse strains and the number of introduced thiols per bacterium can be easily tuned by varying feed ratios. These chemically reactive bacteria are able to spontaneously bond with mucous layer by catalyst-free thiol-disulfide exchange between mucin-associated disulfides and newly converted thiols on bacterial surface and show thiolation level-dependent attachment. Bacteria optimized with 9.3 × 10 thiols per cell achieve 170-fold higher attachment in mucin-enriched jejunum, a challenging location for gut microbiota to colonize. As a proof-of-concept application for microbiota transplantation, covalent bonding-assisted localization of an oral probiotic in the jejunum generates an improved remission of jejunal mucositis. Our findings demonstrate that transforming bacteria with a reactive surface provides an approach to chemically control bacterial localization, which is highly desirable for developing next-generation bacterial living bioagents.
Topics: Disulfides; Sulfhydryl Compounds; Probiotics; Mucins; Bacteria
PubMed: 36528693
DOI: 10.1038/s41467-022-35579-6 -
International Journal of Pharmaceutics Dec 2021Mucoadhesion, adhesion of a material to a mucous membrane or a mucus-covered surface, has been employed in drug delivery to prolong contact with adsorption sites and...
Mucoadhesion, adhesion of a material to a mucous membrane or a mucus-covered surface, has been employed in drug delivery to prolong contact with adsorption sites and consequently a likely improvement of drug absorption. Mucoadhesion in the oral cavity also provides additional effects on tactile mouthfeel and extended flavor delivery, which impact consumer perception. The mechanisms behind mucoadhesion have not been well understood and there are contradictory literature results on the ranking of mucoadhesive properties of different polymers based on what in-vitro methods that are used. We herein examine the molecular interactions of different polymers with mucin from bovine submaxillary glands at pH 6.6 by using H NMR (Nuclear Magnetic Resonance) that provides atomically resolved information on conformational mobility of the mucin. Studying different types of polymers with different chemical structures and degrees of polymerization (DP), we can via the NMR linewidths and the signal intensities distinguish if the polymers interact with specific segments of the mucin or if they have a universal effect on the mobility of all the molecular segments of the mucin. The specific interaction sites on the mucin for positively charged polymer poly(ethyleneimine) are shown to be different from those for negatively and neutrally charged polymers. In addition, the interactions are also driven by the DP, the concentration of the polymers, and the dehydration. Deepened understanding of molecular effects of the different polymers on the mucin can therefore have strong impact on the development of mucoadhesive products in pharmaceutical and food applications. Finally, we raise awareness of the interpretation of rheological data in terms of mucoadhesion.
Topics: Animals; Cattle; Drug Delivery Systems; Mucins; Mucus; Polymers; Rheology
PubMed: 34755651
DOI: 10.1016/j.ijpharm.2021.121245 -
Advanced Drug Delivery Reviews Jan 2022Mucins are an ancient group of glycoproteins that provide viscoelastic, lubricating and hydration properties to fluids bathing wet surfaced epithelia. They are involved... (Review)
Review
Mucins are an ancient group of glycoproteins that provide viscoelastic, lubricating and hydration properties to fluids bathing wet surfaced epithelia. They are involved in the protection of underlying tissues by forming a barrier with selective permeability properties. The expression, processing and spatial distribution of mucins are often determined by organ-specific requirements that in the eye involve protecting against environmental insult while allowing the passage of light. The human ocular surface epithelia have evolved to produce an extremely thin and watery tear film containing a distinct soluble mucin product secreted by goblet cells outside the visual axis. The adaptation to the ocular environment is notably evidenced by the significant contribution of transmembrane mucins to the tear film, where they can occupy up to one-quarter of its total thickness. This article reviews the tissue-specific properties of human ocular mucins, methods of isolation and detection, and current approaches to model mucin systems recapitulating the human ocular surface mucosa. This knowledge forms the fundamental basis to develop applications with a promising biological and clinical impact.
Topics: Animals; Epithelial Cells; Eye; Humans; Mucins; Ocular Physiological Phenomena; Tears; Vision, Ocular
PubMed: 34875287
DOI: 10.1016/j.addr.2021.114074