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Microbes and Infection 2023Influenza A virus (IAV) in the human and swine host infects epithelial cells lining the respiratory tract causing a necrotizing bronchitis and bronchiolitis. These...
Influenza A virus (IAV) in the human and swine host infects epithelial cells lining the respiratory tract causing a necrotizing bronchitis and bronchiolitis. These epithelial surfaces are protected by large glycoproteins called mucins. Mucin 4 (MUC4) is a transmembrane mucin that consists of an alpha subunit responsible for surface protection and intracellular beta subunit involved in signal transduction which repress apoptosis and stimulate epithelial proliferation. This study was designed to determine the expression and potential role of MUC4 during IAV infection. We used immunohistochemistry in combination with machine learning image analysis to quantify differential protein expression of MUC4 subunits in IAV-infected and uninfected lung in a porcine model. MUC4 protein basal expression in control animals varied significantly by litter. MUC4 protein expression was significantly increased in bronchioles with necrotizing bronchiolitis compared to histologically normal bronchioles, likely representing a regenerative response to restore mucosal integrity of conducting airways. Understanding the impact of differential MUC4 expression among healthy individuals and during IAV infection will facilitate control strategies by elucidating mechanisms associated with susceptibility to IAV that can be therapeutically or genetically regulated and may be extended to other respiratory diseases.
Topics: Humans; Animals; Swine; Mucin-4; Mucins; Influenza, Human; Influenza A virus; Lung; Bronchiolitis
PubMed: 37295769
DOI: 10.1016/j.micinf.2023.105169 -
Archives of Pathology & Laboratory... Oct 2006Mucins are glycoproteins produced by both normal and neoplastic glandular epithelial cells including endocervix.
CONTEXT
Mucins are glycoproteins produced by both normal and neoplastic glandular epithelial cells including endocervix.
OBJECTIVE
To determine the expression of mucins in uterine cervical glandular lesions and whether mucin expression correlates with the nature and origin of the glandular lesions.
DESIGN
Antibodies to MUC1, MUC2, MUC4, and MUC5AC were applied on 52 cases including 14 endocervical adenocarcinomas (including 4 adenosquamous carcinomas), 9 endometrial carcinomas (8 endometrioid adenocarcinomas and 1 adenosquamous carcinoma), 8 adenocarcinoma in situ (AIS), 2 glandular dysplasias, 6 tubal metaplasias, 10 microglandular hyperplasias, and 3 normal endocervix. The presence of any staining was considered positive.
RESULTS
All benign endocervical epithelia, including tubal metaplasia and microglandular hyperplasia, expressed MUC1, MUC4, and MUC5AC but not MUC2. Almost all endocervical AIS and carcinomas and all endometrial adenocarcinomas expressed MUC1; the exceptions were 2 cases of endocervical adenocarcinoma and 1 case of adenosquamous carcinoma of the endocervix. MUC2 staining was noted in 25%, 40%, and 22% of AIS, endocervical adenocarcinomas, and endometrial adenocarcinomas, respectively. About 38% of AIS, 75% of endocervical adenocarcinomas, and 44% of endometrial adenocarcinomas expressed MUC4. Half of AIS, most of endocervical adenocarcinomas, and 22% of endometrial adenocarcinomas expressed MUC5AC. The difference in MUC4 and MUC5AC expression between benign endocervical lesions and AIS and the difference in MUC5AC expression between endocervical and endometrial neoplasms were statistically significant.
CONCLUSIONS
Mucin expressions differed among benign endocervical lesions and AIS and among endocervical and endometrial malignancies. These results suggest that mucin staining may potentially be helpful in differentiating various uterine cervical glandular lesions.
Topics: Adenocarcinoma; Carcinoma; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Mucin 5AC; Mucin-1; Mucin-2; Mucin-4; Mucins; Staining and Labeling; Uterine Cervical Diseases; Uterine Cervical Neoplasms
PubMed: 17090193
DOI: 10.5858/2006-130-1510-MEIBAN -
Cancer Reports (Hoboken, N.J.) Aug 2022Breast cancer is a very common cancer that can be severe if not discovered early. The current tools to detect breast cancer need improvement. Cancer has a universal...
BACKGROUND
Breast cancer is a very common cancer that can be severe if not discovered early. The current tools to detect breast cancer need improvement. Cancer has a universal tendency to affect glycosylation. The glycosylation of circulating extracellular vesicle-associated glycoproteins, and mucins may offer targets for detection methods and have been only explored in a limited capacity.
AIM
Our aim was to develop an approach to detect the aberrant glycosylation of mucins and extracellular vesicle-associated glycoproteins from human sera using fluorescent nanoparticles, and preliminarily evaluate this approach for the differential diagnosis of breast cancer.
METHODS AND RESULTS
The assay involved immobilizing glycosylated antigens using monoclonal antibodies and then probing their glycosylation by using lectins and glycan-specific antibodies coated on Eu -doped nanoparticles. Detection of mucin 1 and mucin 16 glycosylation with wheat germ agglutinin, and detection of the extracellular vesicle-associated CD63 were found to have better diagnostic ability for localized breast cancer than the conventional assays for mucin 1 and mucin 16 based tumor markers when the receiver operating characteristics were compared.
CONCLUSIONS
These results indicate that successful differential diagnosis of primary breast cancer may be aided by detecting cancer-associated glycosylation of mucin 1 and mucin 16, and total concentration of CD63, in human serum.
Topics: Biomarkers, Tumor; Breast Neoplasms; CA-125 Antigen; Extracellular Vesicles; Female; Glycoproteins; Glycosylation; Humans; Mucin-1; Mucins
PubMed: 34423573
DOI: 10.1002/cnr2.1540 -
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 -
Chemical Senses Sep 2019Mucins are a key component of the surface mucus overlying airway epithelium. Given the different functions of the olfactory and respiratory epithelia, we hypothesized...
UNLABELLED
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.
LEVEL OF EVIDENCE
N/A (Basic Science Research).IACUC-approved study [Protocol 200065].
Topics: Animals; Cells, Cultured; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mucins; Nasal Mucosa; Respiratory Mucosa
PubMed: 31300812
DOI: 10.1093/chemse/bjz046 -
Archives of Pathology & Laboratory... Nov 2012There are virtually no data in the literature regarding the incidence, patterns, and clinicopathologic characteristics of mucinous carcinomas (MCs) of the gallbladder... (Comparative Study)
Comparative Study
CONTEXT
There are virtually no data in the literature regarding the incidence, patterns, and clinicopathologic characteristics of mucinous carcinomas (MCs) of the gallbladder (GB).
OBJECTIVE
To determine the incidence of mucinous differentiation in invasive GB carcinomas and the clinicopathologic characteristics of those that qualify as MC.
DESIGN
Primary invasive GB carcinomas (n = 606) were reviewed for mucinous differentiation. Some degree of mucin production was identified in 40 cases (6.6%); however, only 15 (2.5%) were qualified for the World Health Organization definition of MC (stromal mucin deposition constituting >50% of the tumor).
RESULTS
The mean age was 65 years, and the female to male ratio was 1.1 (versus 3.9 for conventional pancreatobiliary-type GB adenocarcinomas; P = .04). A significant proportion of the cases (8 of 12, 67%) presented with the clinical picture and intraoperative findings that were interpreted as acute cholecystitis. Mean and median tumor sizes were larger than those of conventional adenocarcinomas (4.8 and 3.4 cm versus 2.9 and 2.5 cm, respectively; P = .01). Most (13 of 15, 87%) cases presented with pT3 tumors (versus 48% for ordinary GB carcinomas; P = .01). Two cases had almost an exclusive colloid pattern (>90% composed of well-defined stromal mucin nodules that contained scanty carcinoma cells, most of which were floating within the mucin). Eight cases were of mixed-mucinous type, showing a mixture of colloid and noncolloid patterns. Five others had prominent signet-ring cells, both floating within the mucin (which constituted >50% of the tumor by definition) and infiltrating into the stroma as individual signet-ring cells in some areas. Immunohistochemical analysis performed on the 7 cases that had available tissue revealed CK7 in 4 of 7 (57%), CK20 in 2 of 7 (29%), MUC1 in 4 of 7 (57%), MUC2 in 6 of 7 (86%), CDX2 in 1 of 7 (14%), MUC5AC in 6 of 7 (86%), MUC6 in 0 of 7 (0%), and loss of E-cadherin in 6 of 7 (86%). The MLH1 and MSH2 were retained in 6 of 7 cases (100%). Follow-up information was available for 13 cases: 11 (85%) died of disease (1-37 months) and 2 (15%) were alive (23 months and 1 month). Overall survival of MCs was significantly worse than that of conventional adenocarcinomas (13 versus 26 months; P = .01); however, that did not seem to be independent of stage.
CONCLUSIONS
Mucinous carcinomas constitute 2.5% of GB carcinomas. They present with an acute cholecystitis-type picture. Most MCs are a mixed-mucinous, not pure colloid, type. They are typically large and advanced tumors at the time of diagnosis and thus exhibit more-aggressive behavior than do ordinary GB carcinomas. Immunophenotypically, they differ from conventional GB adenocarcinomas by MUC2 positivity, from intestinal carcinomas by an often inverse CK7/20 profile, from pancreatic mucinous carcinomas by CDX2 negativity, and from mammary colloid carcinomas by a lack of MUC6. Unlike gastrointestinal MCs, they appear to be microsatellite stable.
Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Biomarkers, Tumor; CDX2 Transcription Factor; Cell Differentiation; Female; Gallbladder Neoplasms; Gastrointestinal Neoplasms; Homeodomain Proteins; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Male; Middle Aged; Mucin-2; Mucin-6; Mucins; Neoplasm Invasiveness; Pancreatic Neoplasms
PubMed: 23106580
DOI: 10.5858/arpa.2011-0447-OA -
Journal of Colloid and Interface Science Apr 2024The mucoadhesive characteristics of amphoteric polymers (also known as polyampholytes) can vary and are influenced by factors such as the solution's pH and its relative...
The mucoadhesive characteristics of amphoteric polymers (also known as polyampholytes) can vary and are influenced by factors such as the solution's pH and its relative position against their isoelectric point (pH). Whilst the literature contains numerous reports on mucoadhesive properties of either cationic or anionic polymers, very little is known about these characteristics for polyampholytes EXPERIMENTS: Here, two amphoteric polymers were synthesized by reaction of linear polyethylene imine (l-PEI) with succinic or phthalic anhydride and their mucoadhesive properties were compared to bovine serum albumin (BSA), selected as a natural polyampholyte. Interactions between these polymers and porcine gastric mucin were studied using turbidimetric titration and isothermal titration calorimetry across a wide range of pHs. Model tablets were designed, coated with these polymers and tested to evaluate their adhesion to porcine gastric mucosa at different pHs. Moreover, a retention study using fluorescein isothiocyanate (FITC)-labelled polyampholytes deposited onto mucosal surfaces was also conducted FINDINGS: All these studies indicated the importance of solution pH and its relative position against pH in the mucoadhesive properties of polyampholytes. Both synthetic and natural polyampholytes exhibited strong interactions with mucin and good mucoadhesive properties at pH < pH.
Topics: Swine; Animals; Polymers; Mucins; Gastric Mucins
PubMed: 38218088
DOI: 10.1016/j.jcis.2023.12.176 -
Cancer Letters Dec 2022Mucin MUC4 is an aberrantly expressed oncogene in pancreatic ductal adenocarcinoma (PDAC), yet no pharmacological inhibitors have been identified to target MUC4. Here,...
Mucin MUC4 is an aberrantly expressed oncogene in pancreatic ductal adenocarcinoma (PDAC), yet no pharmacological inhibitors have been identified to target MUC4. Here, we adapted an in silico screening method using the Cancer Therapeutic Response Database (CTRD) to Identify Small Molecule Inhibitors against Mucins (SMIMs). We identified Bosutinib as a candidate drug to target oncogenic mucins among 126 FDA-approved drugs from CTRD screening. Functionally, Bosutinib treatment alone/and in combination with gemcitabine (Gem)/5' fluorouracil (5FU) reduced in vitro viability, migration, and colony formation in multiple PDAC cell lines as well as human PDAC organoid prolifertaion and growth and in vivo xenograft growth. Further, biochemical and molecular analyses showed that Bosutinib exhibited these functional effects by downregulating MUC4 mucin at both transcript and translation levels in a dose- and time-dependent manner. Mechanistically, global transcriptome analysis in PDAC cells upon treatment with Bosutinib revealed disruption of the Src-ERK/AKT-FosL1 pathway, leading to decreased expression of MUC4 and MUC5AC mucins. Taken together, Bosutinib is a promising, novel, and highly potent SMIMs to target MUC4/MUC5AC mucins. This mucin-targeting effect of Bosutinib can be exploited in the future with cytotoxic agents to treat mucinous tumors.
Topics: Humans; Gemcitabine; Mucins; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Cell Line, Tumor; Mucin-4
PubMed: 36285687
DOI: 10.1016/j.canlet.2022.215922 -
International Journal of Medical... 2017Pseudomyxoma peritonei (PMP) is a rare disease with excess intraperitoneal mucin secretion. Treatment involves laparotomy, cytoreduction and chemotherapy that is very...
Pseudomyxoma peritonei (PMP) is a rare disease with excess intraperitoneal mucin secretion. Treatment involves laparotomy, cytoreduction and chemotherapy that is very invasive with patients often acquiring numerous compromises. Hence a mucolytic comprising of bromelain and N-acetyl cystein has been developed to solubilise mucin in situ for removal by catherization. Owing to differences in mucin appearance and hardness, dissolution varies. Therefore the current study investigates the inter-mucin physical and chemical characteristics, in order to reformulate an effective mucolytic for all mucin. PMP mucin, from the three categories (soft, semi hard and hard mucin) was solubilised and then various physical characteristics such as turbidity, density, kinematic viscosity were measured. The water content and the density of solid mucin were also determined. This was followed by the determination of sialic acid, glucose, lipid, Thiol (S-S and S-H) content of the samples. Lastly, the distribution of MUC2, MUC5B and MUC5AC was determined using western blot technique. Both turbidity and kinematic viscosity and sialic acid content increased linearly as the hardness of mucin increased. However, density, hydration, protein, glucose, lipid and sulfhydryl and disulphide content decreased linearly as hardness of mucin increased. The distribution ratio of mucins (MUC2:MUC5B:MUC5AC) in soft mucin is 2.25:1.5:1.0, semi hard mucin is 1:1:1 and hard mucin is 3:2:1. The difference in texture and hardness of mucin may be due to cellular content, hydration, glucose, protein, lipids, thiol and MUC distribution. Soft mucin is solely made of glycoprotein whilst the others contained cellular materials.
Topics: Glucose; Humans; Lipids; Mucin 5AC; Mucin-2; Mucin-5B; Mucins; Mucus; N-Acetylneuraminic Acid; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Sulfhydryl Compounds; Viscosity
PubMed: 28138305
DOI: 10.7150/ijms.16422 -
NPJ Biofilms and Microbiomes Dec 2023Understanding how dietary polysaccharides affect mucin O-glycosylation and gut microbiota could provide various nutrition-based treatments. Here, the O-glycan profile of...
Understanding how dietary polysaccharides affect mucin O-glycosylation and gut microbiota could provide various nutrition-based treatments. Here, the O-glycan profile of the colonic mucosa and gut microbiome were investigated in C57BL/6J mice fed six structurally diverse dietary polysaccharides and a mixture of six fibers. Dietary polysaccharides increased total O-glycans, mainly by stimulating neutral glycans. Highly branched arabinogalactan promoted terminally fucosylated core 1 O-glycans; whereas linear polysaccharides, including pectin, konjac glucomannan, inulin, and the fiber mixture, favored terminally di-fucosylated O-glycans. The last three polysaccharides also lowered the level of sulfated O-glycans and sialylated mono-fucosylated O-glycans. Varied monosaccharide composition in mixed polysaccharides had a synergistic beneficial effect, boosting fucosylated neutral glycans, decreasing acidic glycans, and stimulating microbial richness and diversity. Dietary polysaccharides containing arabinose and sulfate groups enhanced the relative abundances of Akkermansia and Muribaculaceae, respectively. The present comparison reveals the relationship between dietary polysaccharide structure, mucin O-glycan composition, and intestinal microorganisms.
Topics: Animals; Mice; Mucins; Gastrointestinal Microbiome; Glycosylation; Mice, Inbred C57BL; Polysaccharides
PubMed: 38081891
DOI: 10.1038/s41522-023-00468-3