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Frontiers in Immunology 2024The Mucin (MUC) family, a range of highly glycosylated macromolecules, is ubiquitously expressed in mammalian epithelial cells. Such molecules are pivotal in... (Review)
Review
The Mucin (MUC) family, a range of highly glycosylated macromolecules, is ubiquitously expressed in mammalian epithelial cells. Such molecules are pivotal in establishing protective mucosal barriers, serving as defenses against pathogenic assaults. Intriguingly, the aberrant expression of specific MUC proteins, notably Mucin 1 (MUC1) and Mucin 16 (MUC16), within tumor cells, is intimately associated with oncogenesis, proliferation, and metastasis. This association involves various mechanisms, including cellular proliferation, viability, apoptosis resistance, chemotherapeutic resilience, metabolic shifts, and immune surveillance evasion. Due to their distinctive biological roles and structural features in oncology, MUC proteins have attracted considerable attention as prospective targets and biomarkers in cancer therapy. The current review offers an exhaustive exploration of the roles of MUC1 and MUC16 in the context of cancer biomarkers, elucidating their critical contributions to the mechanisms of cellular signal transduction, regulation of immune responses, and the modulation of the tumor microenvironment. Additionally, the article evaluates the latest advances in therapeutic strategies targeting these mucins, focusing on innovations in immunotherapies and targeted drugs, aiming to enhance customization and accuracy in cancer treatments.
Topics: Animals; Mucin-1; CA-125 Antigen; Mucins; Neoplasms; Immunity; Mammals; Tumor Microenvironment
PubMed: 38361923
DOI: 10.3389/fimmu.2024.1356913 -
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 -
Bioscience Reports Oct 2022Protein glycosylation is ubiquitous throughout biology. From bacteria to humans, this post translational modification with sophisticated carbohydrate structures plays a... (Review)
Review
Protein glycosylation is ubiquitous throughout biology. From bacteria to humans, this post translational modification with sophisticated carbohydrate structures plays a profound role in the interaction of proteins with cells and changes the physiochemical properties of the proteins that carry them. When the glycans are linked to Ser or Thr residues, they are known as O-linked glycans, as the glycosidic linkage is through oxygen. O-glycans are perhaps best known as part of the mucin proteins, however many soluble proteins carry these types of glycans, and that their roles in biology are still being discovered. Many of the soluble proteins that carry O-glycans have a role as therapeutic proteins, and in the 21st century, the application of synthetic biology is starting to be applied to improving these proteins through manipulation of the glycans. This review will explore the role of these O-linked glycans in proteins with pharmaceutical significance, as well as recent advancements in recombinant glycoprotein therapeutics.
Topics: Humans; Glycosylation; Polysaccharides; Mucins; Protein Processing, Post-Translational; Recombinant Proteins
PubMed: 36214107
DOI: 10.1042/BSR20220094 -
Gut Mar 2023Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of...
OBJECTIVE
Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.
DESIGN
Targeted and whole-genome low-coverage sequencing, genome-wide methylation and transcriptome analyses were applied on a final collective of 122 morphologically well-characterised low-grade and high-grade PDAC precursors, including intestinal and gastric intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasias (PanIN).
RESULTS
Epigenetic regulation of mucin genes determines the phenotype of PDAC precursors. PanIN and gastric IPMN display a ductal molecular profile and numerous similarly regulated pathways, including the Notch pathway, but can be distinguished by recurrent deletions and differential methylation and, in part, by the expression of mucin-like 3. Intestinal IPMN are clearly distinct lesions at the molecular level with a more instable genotype and are possibly related to a different ductal cell compartment.
CONCLUSIONS
PDAC precursors with gastric and intestinal phenotype are heterogeneous in terms of morphology, genetic and epigenetic profile. This heterogeneity is related to a different cell identity and, possibly, to a different aetiology.
Topics: Humans; Epigenesis, Genetic; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Mucins; Phenotype
PubMed: 35944927
DOI: 10.1136/gutjnl-2021-326550 -
The Kaohsiung Journal of Medical... Sep 2020
Topics: Adenocarcinoma, Mucinous; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Cholangiocarcinoma; Gene Expression; Humans; Keratin-7; Magnetic Resonance Imaging; Male; Middle Aged; Mucin 5AC; Mucin-2; Mucin-6; Tomography, X-Ray Computed
PubMed: 32492241
DOI: 10.1002/kjm2.12242 -
Gut Microbes 2021An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer.... (Review)
Review
An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host and gut microbiota different dietary patterns (prebiotics and probiotics) is needed to maintain mucus composition, mucin synthesis, and regulation. Here, we review how the interactions between diet and gut microbiota and bacterial metabolites () regulate mucus layer functionalities and mucin expression in human health and disease.
Topics: Animals; Colorectal Neoplasms; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mucins; Prebiotics; Probiotics
PubMed: 34586012
DOI: 10.1080/19490976.2021.1974795 -
Annals of the American Thoracic Society Nov 2018Mucociliary clearance is a crucial component of innate defense of the lung. In respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and cystic... (Review)
Review
Mucociliary clearance is a crucial component of innate defense of the lung. In respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis, mucus with abnormal properties contributes to obstruction of the airways. The failure in function of mucus in airway clearance and pathogen protection leads to chronic infection and risk of death. Polymeric mucins (MUC5AC and MUC5B) provide the structural framework of the airway mucus gel. The intracellular synthesis and assembly of these enormous, polymeric O-linked glycoproteins is a complex, multistage process involving intra- and intermolecular disulfide bond formation and extensive addition of O-glycan chains. The fully formed polymers are packaged in a highly organized and condensed form within secretory granules inside specialized secretory cells, and after the appropriate stimulus, mucins are released and expand to form mucus. This short article brings together the current knowledge on the different steps in the production of mucin polymers and the molecular mechanisms that condense them into a packaged form in secretory granules. It is by unraveling the molecular mechanisms that control intracellular mucin supramolecular structure that we might gain new insight into what determines mucus gel properties in health and disease.
Topics: Humans; Lung Diseases; Mucins; Mucociliary Clearance; Secretory Vesicles
PubMed: 30431345
DOI: 10.1513/AnnalsATS.201802-143AW -
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 -
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 -
Nature Communications Jun 2023Agonist-mediated stimulated pathway of mucin and insulin release are biphasic in which rapid fusion of pre-docked granules is followed by slow docking and fusion of...
Agonist-mediated stimulated pathway of mucin and insulin release are biphasic in which rapid fusion of pre-docked granules is followed by slow docking and fusion of granules from the reserve pool. Here, based on a cell-culture system, we show that plasma membrane-located tetraspanin-8 sequesters syntaxin-2 to control mucin release. Tetraspanin-8 affects fusion of granules during the second phase of stimulated mucin release. The tetraspanin-8/syntaxin-2 complex does not contain VAMP-8, which functions with syntaxin-2 to mediate granule fusion. We suggest that by sequestering syntaxin-2, tetraspanin-8 prevents docking of granules from the reserve pool. In the absence of tetraspanin-8, more syntaxin-2 is available for docking and fusion of granules and thus doubles the quantities of mucins secreted. This principle also applies to insulin release and we suggest a cell type specific Tetraspanin/Syntaxin combination is a general mechanism regulating the fusion of dense core granules.
Topics: Syntaxin 1; Islets of Langerhans; Insulin Secretion; Exocytosis; Insulin; Mucins; Cytoplasmic Granules
PubMed: 37349283
DOI: 10.1038/s41467-023-39277-9