-
Macromolecular Bioscience Aug 2017The present review is aimed at elucidating relatively new aspects of mucoadhesion/mucus interaction and related phenomena that emerged from a Mucoadhesion workshop held... (Review)
Review
The present review is aimed at elucidating relatively new aspects of mucoadhesion/mucus interaction and related phenomena that emerged from a Mucoadhesion workshop held in Munster on 2-3 September 2015 as a satellite event of the ICCC 13th-EUCHIS 12th. After a brief outline of the new issues, the focus is on mucus description, purification, and mucus/mucin characterization, all steps that are pivotal to the understanding of mucus related phenomena and the choice of the correct mucosal model for in vitro and ex vivo experiments, alternative bio/mucomimetic materials are also presented. Then a selection of preparative techniques and testing methods are described (at molecular as well as micro and macroscale) that may support the pharmaceutical development of mucus interactive systems and assist formulators in the scale-up and industrialization steps. Recent applications of mucoadhesive systems (including medical devices) intended for different routes of administration (oral, gastrointestinal, vaginal, nasal, ocular, and intravesical) and for the treatment of difficult to treat pathologies or the alleviation of symptoms are described.
Topics: Animals; Biomedical Research; Biomimetic Materials; Humans; Mucins; Mucus
PubMed: 28378910
DOI: 10.1002/mabi.201600534 -
Nature Chemical Biology Jul 2022Mucins are large gel-forming polymers inside the mucus barrier that inhibit the yeast-to-hyphal transition of Candida albicans, a key virulence trait of this important...
Mucins are large gel-forming polymers inside the mucus barrier that inhibit the yeast-to-hyphal transition of Candida albicans, a key virulence trait of this important human fungal pathogen. However, the molecular motifs in mucins that inhibit filamentation remain unclear despite their potential for therapeutic interventions. Here, we determined that mucins display an abundance of virulence-attenuating molecules in the form of mucin O-glycans. We isolated and cataloged >100 mucin O-glycans from three major mucosal surfaces and established that they suppress filamentation and related phenotypes relevant to infection, including surface adhesion, biofilm formation and cross-kingdom competition between C. albicans and the bacterium Pseudomonas aeruginosa. Using synthetic O-glycans, we identified three structures (core 1, core 1 + fucose and core 2 + galactose) that are sufficient to inhibit filamentation with potency comparable to the complex O-glycan pool. Overall, this work identifies mucin O-glycans as host molecules with untapped therapeutic potential to manage fungal pathogens.
Topics: Candida albicans; Fucose; Mucins; Polysaccharides; Virulence
PubMed: 35668191
DOI: 10.1038/s41589-022-01035-1 -
Nature Chemical Biology Jun 2023Mucinolytic bacteria modulate host-microbiota symbiosis and dysbiosis through their ability to degrade mucin O-glycans. However, how and to what extent bacterial enzymes...
Mucinolytic bacteria modulate host-microbiota symbiosis and dysbiosis through their ability to degrade mucin O-glycans. However, how and to what extent bacterial enzymes are involved in the breakdown process remains poorly understood. Here we focus on a glycoside hydrolase family 20 sulfoglycosidase (BbhII) from Bifidobacterium bifidum, which releases N-acetylglucosamine-6-sulfate from sulfated mucins. Glycomic analysis showed that, in addition to sulfatases, sulfoglycosidases are involved in mucin O-glycan breakdown in vivo and that the released N-acetylglucosamine-6-sulfate potentially affects gut microbial metabolism, both of which were also supported by a metagenomic data mining analysis. Enzymatic and structural analysis of BbhII reveals the architecture underlying its specificity and the presence of a GlcNAc-6S-specific carbohydrate-binding module (CBM) 32 with a distinct sugar recognition mode that B. bifidum takes advantage of to degrade mucin O-glycans. Comparative analysis of the genomes of prominent mucinolytic bacteria also highlights a CBM-dependent O-glycan breakdown strategy used by B. bifidum.
Topics: Mucins; Ecosystem; Polysaccharides; Bacteria
PubMed: 36864192
DOI: 10.1038/s41589-023-01272-y -
Advanced Drug Delivery Reviews May 2022The secreted mucus layer that lines and protects epithelial cells is conserved across diverse species. While the exact composition of this protective layer varies... (Review)
Review
The secreted mucus layer that lines and protects epithelial cells is conserved across diverse species. While the exact composition of this protective layer varies between organisms, certain elements are conserved, including proteins that are heavily decorated with N-acetylgalactosamine-based sugars linked to serines or threonines (O-linked glycosylation). These heavily O-glycosylated proteins, known as mucins, exist in many forms and are able to form hydrated gel-like structures that coat epithelial surfaces. In vivo studies in diverse organisms have highlighted the importance of both the mucin proteins as well as their constituent O-glycans in the protection and health of internal epithelia. Here, we summarize in vivo approaches that have shed light on the synthesis and function of these essential components of mucus.
Topics: Epithelial Cells; Glycosylation; Humans; Mucins; Mucus; Polysaccharides
PubMed: 35278522
DOI: 10.1016/j.addr.2022.114182 -
The FEBS Journal Jan 2010The O-glycosylation of Ser and Thr by N-acetylgalactosamine-linked (mucin-type) oligosaccharides is often overlooked in protein analysis. Three characteristics make... (Review)
Review
The O-glycosylation of Ser and Thr by N-acetylgalactosamine-linked (mucin-type) oligosaccharides is often overlooked in protein analysis. Three characteristics make O-linked glycosylation more difficult to analyse than N-linked glycosylation, namely: (a) no amino acid consensus sequence is known; (b) there is no universal enzyme for the release of O-glycans from the protein backbone; and (c) the density and number of occupied sites may be very high. For significant biological conclusions to be drawn, the complete picture of O-linked glycosylation on a protein needs to be determined. This review specifically addresses the analytical approaches that have been used, and the challenges remaining, in the characterization of both the composition and structure of mucin-type O-glycans, and the determination of the occupancy and heterogeneity at each amino acid attachment site.
Topics: Animals; Carbohydrate Sequence; Glycopeptides; Glycosylation; Humans; Molecular Sequence Data; Molecular Structure; Mucins; Polysaccharides; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry
PubMed: 19919547
DOI: 10.1111/j.1742-4658.2009.07429.x -
Journal of Medicine and Life 2017Colorectal cancer (CRC) is a major health problem worldwide. The objective of our study was to assess the histopathological (HP) and immunohistochemical (IHC) profile of...
Colorectal cancer (CRC) is a major health problem worldwide. The objective of our study was to assess the histopathological (HP) and immunohistochemical (IHC) profile of mucins from signet ring (SR) and mucinous rectal carcinoma, while evaluating their value as a prognostic factor and muco-secretive ability. The HP study (76 cases) included 4 categories of patients: pure mucinous (PM), mixed mucinous components (MM) (50-80% of the tumor cells), mixed mucinous components (Mm) (< 50% of the tumor cells) and signet ring (SR). The IHC study consisted of a total of 30 cases of MRC and was processed by the ABC/ HRP technique. The antibodies used have addressed their muco-secretive capacity: MUC1, 2 and MUC5AC. MRC cases were more frequent in the sixth decade, with a median age of 57.3 years. It could be noted that MRC tended to develop at younger ages. For the MP variant, the gender ratio was 1.37 in favor of men, while for the MM variant it was 1.16, 1.31 for the Mm and 1.6 in the case of signet ring type. Most of the MRC were moderately differentiated forms, except for the SR form, poorly differentiated forms predominating. Well-differentiated forms were the most underrepresented, being more common in the Mm version. Regarding the biochemical type of mucin, MP and SR were characterized by acid mucins and sialomucin, while in the Mm type, there was a balance of acidic and neutral mucins. The prevalence of mucin acids, respectively sulfomucin, was characteristic to younger ages and poor prognosis.
Topics: Adenocarcinoma, Mucinous; Goblet Cells; Humans; Immunohistochemistry; Middle Aged; Mucin 5AC; Mucins; Rectal Neoplasms
PubMed: 28616090
DOI: No ID Found -
American Journal of Respiratory and... Nov 2022
Topics: Humans; Mucin-5B; Mucin 5AC; Secretory Vesicles
PubMed: 35938865
DOI: 10.1164/rccm.202208-1459ED -
BMB Reports Jul 2021Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling... (Review)
Review
Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling transduction, and tissue homeostasis. Abnormality of mucus expression and structure contributes to biological properties related to human cancer progression. Tumor growth sites induce inhospitable conditions. Many kinds of research suggest that mucins provide a microenvironment to avoid hypoxia, acidic, and other biological conditions that promote cancer progression. Given that the mucus layer captures growth factors or cytokines, we propose that mucin helps to ameliorate inhospitable conditions in tumor-growing sites. Additionally, the composition and structure of mucins enable them to mimic the surface of normal epithelial cells, allowing tumor cells to escape from immune surveillance. Indeed, human cancers such as mucinous carcinoma, show a higher incidence of invasion to adjacent organs and lymph node metastasis than do non-mucinous carcinoma. In this minireview, we discuss how mucin provides a tumor-friendly environment and contributes to increased cancer malignancy in mucinous carcinoma. [BMB Reports 2021; 54(7): 344-355].
Topics: Biomarkers, Tumor; Humans; Mucin-1; Mucins; Neoplasms; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 34154702
DOI: 10.5483/BMBRep.2021.54.7.064 -
International Journal of Molecular... Jun 2019Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first... (Review)
Review
Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first barrier against external pollutants, the intestinal mucosa is protected by a mechanical barrier, chemical barrier, immune barrier, and biological barrier. Firstly, mycotoxins can disrupt the mechanical barrier function of the intestinal mucosa, by destroying the morphology and tissue integrity of the intestinal epithelium. Secondly, mycotoxins can cause changes in the composition of mucin monosaccharides and the expression of intestinal mucin, which in turn affects mucin function. Thirdly, mycotoxins can cause damage to the intestinal mucosal immune barrier function. Finally, the microbiotas of animals closely interact with ingested mycotoxins. Based on existing research, this article reviews the effects of mycotoxins on the intestinal mucosal barrier and its mechanisms.
Topics: Animals; Humans; Immunity, Innate; Intestinal Mucosa; Mucins; Mycotoxins
PubMed: 31174254
DOI: 10.3390/ijms20112777 -
Cancer Metastasis Reviews Sep 2020A dynamic mucosal layer shields the epithelial cells lining the body cavities and is made up of high molecular weight, heavily glycosylated, multidomain proteins called... (Review)
Review
A dynamic mucosal layer shields the epithelial cells lining the body cavities and is made up of high molecular weight, heavily glycosylated, multidomain proteins called mucins. Mucins, broadly grouped into transmembrane and secreted mucins, are the first responders to any mechanical or chemical insult to the epithelia and help maintain tissue homeostasis. However, their intrinsic properties to protect and repair the epithelia are exploited during oncogenic processes, where mucins are metamorphosed to aid the tumor cells in their malignant journey. Diverse domains, like the variable number tandem repeats (VNTR), sea urchin sperm protein enterokinase and agrin (SEA), adhesion-associated domain (AMOP), nidogen-like domain (NIDO), epidermal growth factor-like domain (EGF), and von Willebrand factor type D domain (vWD) on mucins, including MUC1, MUC4, MUC5AC, MUC5B, and MUC16, have been shown to facilitate cell-to-cell and cell-to-matrix interactions, and cell-autonomous signaling to promote tumorigenesis and distant dissemination of tumor cells. Several obstacles have limited the study of mucins, including technical difficulties in working with these huge glycoproteins, the dearth of scientific tools, and lack of animal models; thus, the tissue-dependent and domain-specific roles of mucins during mucosal protection, chronic inflammation, tumorigenesis, and hematological dissemination of malignant cells are still unclear. Future studies should try to integrate information on the rheological, molecular, and biological characteristics of mucins to comprehensively delineate their pathophysiological role and evaluate their suitability as targets in future diagnostic and therapeutic strategies.
Topics: Animals; Humans; Mucins; Neoplasm Metastasis; Neoplasms; Protein Domains
PubMed: 32488403
DOI: 10.1007/s10555-020-09896-5