{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:27:51Z","timestamp":1791430071032,"version":"4.3.3"},"reference-count":113,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>MUC2 mucin, the primary gel-forming component of intestinal mucus, is well researched and a model of polymerisation and post-secretory organisation has been published previously. Recently, several significant developments have been made which either introduce new ideas or challenge previous theories. New ideas include an overhaul of the MUC2 C-terminal globular structure which is proposed to harbour several previously unobserved domains, and include a site for an extra intermolecular disulphide bridge dimer between the cysteine 4379 of adjacent MUC2 C-termini. MUC2 polymers are also now thought to be secreted attached to the epithelial surface of goblet cells in the small intestine and removed following secretion via a metalloprotease meprin \u03b2-mediated cleavage of the von Willebrand D2 domain of the N-terminus. It remains unclear whether MUC2 forms intermolecular dimers, trimers, or both, at the N-termini during polymerisation, with several articles supporting either trimer or dimer formation. The presence of a firm inner mucus layer in the small intestine is similarly unclear. Considering this recent research, this review proposes an update to the previous model of MUC2 polymerisation and secretion, considers conflicting theories and data, and highlights the importance of this research to the understanding of MUC2 mucus layers in health and disease.<\/jats:p>","DOI":"10.3390\/polym16121663","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T04:30:12Z","timestamp":1718253012000},"page":"1663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The MUC2 Gene Product: Polymerisation and Post-Secretory Organisation\u2014Current Models"],"prefix":"10.3390","volume":"16","author":[{"given":"Kyle J.","family":"Stanforth","sequence":"first","affiliation":[{"name":"Aelius Biotech, The Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4617-3235","authenticated-orcid":false,"given":"Maria I.","family":"Zakhour","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Newcastle University Biosciences Institute, Catherine Cookson Building, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8679-0004","authenticated-orcid":false,"given":"Peter I.","family":"Chater","sequence":"additional","affiliation":[{"name":"Aelius Biotech, The Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Aelius Biotech, The Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Adamson","sequence":"additional","affiliation":[{"name":"Aelius Biotech, The Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh A.","family":"Robson","sequence":"additional","affiliation":[{"name":"Aelius Biotech, The Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Newcastle University Biosciences Institute, Catherine Cookson Building, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3109\/00365521.2014.898326","article-title":"Surface area of the digestive tract\u2013revisited","volume":"49","author":"Helander","year":"2014","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13756-021-00903-0","article-title":"Emergence of nosocomial associated opportunistic pathogens in the gut microbiome after antibiotic treatment","volume":"10","author":"Raplee","year":"2021","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rath, S., Rud, T., Karch, A., Pieper, D.H., and Vital, M. (2018). Pathogenic functions of host microbiota. Microbiome, 6.","DOI":"10.1186\/s40168-018-0542-0"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1128\/CMR.00054-05","article-title":"Pathogenesis of Helicobacter pylori infection","volume":"19","author":"Kusters","year":"2006","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1111\/j.1572-0241.2001.04159.x","article-title":"Esophageal mucin: An adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett\u2019s esophagus","volume":"96","author":"Dixon","year":"2001","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.cell.2020.09.021","article-title":"Assembly mechanism of mucin and von Willebrand factor polymers","volume":"183","author":"Javitt","year":"2020","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"229","DOI":"10.4155\/tde-2015-0002","article-title":"The properties of the mucus barrier, a unique gel\u2014How can nanoparticles cross it?","volume":"7","author":"Pearson","year":"2016","journal-title":"Ther. Deliv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.bbagen.2014.05.003","article-title":"Mucins: A biologically relevant glycan barrier in mucosal protection","volume":"1850","author":"Corfield","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.addr.2008.09.012","article-title":"Micro-and macrorheology of mucus","volume":"61","author":"Lai","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","first-page":"AC01","article-title":"Analysis of the distribution of mucins in adult human gastric mucosa and its functional significance","volume":"10","author":"Prasanna","year":"2016","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s10719-015-9606-6","article-title":"Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases","volume":"32","author":"Behera","year":"2015","journal-title":"Glycoconj. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrmicro2538","article-title":"Mucin dynamics and enteric pathogens","volume":"9","author":"McGuckin","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.ijpharm.2017.09.018","article-title":"Physicochemical properties of mucus and their impact on transmucosal drug delivery","volume":"532","author":"Leal","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"a014159","DOI":"10.1101\/cshperspect.a014159","article-title":"Perspectives on mucus properties and formation\u2014Lessons from the biochemical world","volume":"2","author":"Ambort","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1042\/BJ20102066","article-title":"Function of the CysD domain of the gel-forming MUC2 mucin","volume":"436","author":"Ambort","year":"2011","journal-title":"Biochem. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s12033-012-9562-3","article-title":"Increased understanding of the biochemistry and biosynthesis of MUC2 and other gel-forming mucins through the recombinant expression of their protein domains","volume":"54","author":"Ambort","year":"2013","journal-title":"Mol. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1084\/jem.20120562","article-title":"Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype","volume":"209","author":"Gustafsson","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1016\/j.jmb.2014.04.027","article-title":"Intestinal MUC2 mucin supramolecular topology by packing and release resting on D3 domain assembly","volume":"426","author":"Nilsson","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1016\/j.jmb.2019.07.018","article-title":"Intestinal gel-forming mucins polymerize by disulfide-mediated dimerization of d3 domains","volume":"431","author":"Javitt","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1038\/s41467-023-37666-8","article-title":"The intestinal MUC2 mucin C-terminus is stabilized by an extra disulfide bond in comparison to von Willebrand factor and other gel-forming mucins","volume":"14","author":"Gallego","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_21","first-page":"5958","article-title":"In vitro modelling of the mucosa of the oesophagus and upper digestive tract","volume":"5","author":"Stanforth","year":"2021","journal-title":"Ann. Esophagus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1172\/JCI26705","article-title":"MUC1 cell surface mucin is a critical element of the mucosal barrier to infection","volume":"117","author":"McAuley","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/omi.12113","article-title":"Absence of capsule reveals glycan-mediated binding and recognition of salivary mucin MUC7 by Streptococcus pneumoniae","volume":"31","author":"Thamadilok","year":"2016","journal-title":"Mol. Oral Microbiol."},{"key":"ref_24","first-page":"63","article-title":"Regulation of human MUC7 mucin gene expression by cigarette smoke extract or cigarette smoke and Pseudomonas aeruginosa lipopolysaccharide in human airway epithelial cells and in MUC7 transgenic mice","volume":"4","author":"Fan","year":"2010","journal-title":"Open Respir. Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cha, H.-J., and Song, K.S. (2018). Effect of MUC8 on airway inflammation: A friend or a foe?. J. Clin. Med., 7.","DOI":"10.3390\/jcm7020026"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32556","DOI":"10.1038\/srep32556","article-title":"The C-terminal region of OVGP1 remodels the zona pellucida and modifies fertility parameters","volume":"6","author":"Algarra","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1146\/annurev.physiol.70.113006.100702","article-title":"Structure and function of the polymeric mucins in airways mucus","volume":"70","author":"Thornton","year":"2008","journal-title":"Annu. Rev. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17503","DOI":"10.1038\/s41598-018-35499-w","article-title":"The central exons of the human MUC2 and MUC6 mucins are highly repetitive and variable in sequence between individuals","volume":"8","author":"Svensson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1074\/jbc.272.6.3168","article-title":"Human mucin gene MUC5B, the 10.7-kb large central exon encodes various alternate subdomains resulting in a super-repeat structural evidence for a 11p15. 5 gene family","volume":"272","author":"Desseyn","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/carcin\/bgy019","article-title":"Ramifications of secreted mucin MUC5AC in malignant journey: A holistic view","volume":"39","author":"Krishn","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hasnain, S.Z., Dawson, P.A., Lourie, R., Hutson, P., Tong, H., Grencis, R.K., McGuckin, M.A., and Thornton, D.J. (2017). Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006218"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2107896118","DOI":"10.1073\/pnas.2107896118","article-title":"Glycocalyx crowding with mucin mimetics strengthens binding of soluble and virus-associated lectins to host cell glycan receptors","volume":"118","author":"Honigfort","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1021\/jp311968b","article-title":"Water sorption and glass transition of pig gastric mucin studied by QCM-D","volume":"117","author":"Znamenskaya","year":"2013","journal-title":"J. Phys. Chem. B"},{"key":"ref_34","first-page":"318","article-title":"Intestinal Muc2 mucin O-glycosylation is affected by microbiota and regulated by differential expression of glycosyltranferases","volume":"27","author":"Arike","year":"2017","journal-title":"Glycobiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1093\/glycob\/cwr182","article-title":"Control of mucin-type O-glycosylation: A classification of the polypeptide GalNAc-transferase gene family","volume":"22","author":"Bennett","year":"2012","journal-title":"Glycobiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/10409239891204198","article-title":"Concepts and principles of O-linked glycosylation","volume":"33","author":"Steen","year":"1998","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/S0006-3495(01)76074-2","article-title":"Database analysis of O-glycosylation sites in proteins","volume":"80","author":"Christlet","year":"2001","journal-title":"Biophys. J."},{"key":"ref_38","first-page":"315","article-title":"6.11\u2014Biosynthesis of Complex Mucin-Type O-Glycans","volume":"Volume 6","author":"Mander","year":"2010","journal-title":"Comprehensive Natural Products II"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1136\/gut.44.3.387","article-title":"Sulphation and secretion of the predominant secretory human colonic mucin MUC2 in ulcerative colitis","volume":"44","author":"Einerhand","year":"1999","journal-title":"Gut"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14657","DOI":"10.1016\/S0021-9258(17)42653-6","article-title":"The thermal depolymerization of porcine submaxillary mucin","volume":"259","author":"Shogren","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1042\/bj3640191","article-title":"Gastric MUC5AC and MUC6 are large oligomeric mucins that differ in size, glycosylation and tissue distribution","volume":"364","author":"Nordman","year":"2002","journal-title":"Biochem. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1165\/rcmb.2010-0312OC","article-title":"Cloning and characterization of human MUC19 gene","volume":"45","author":"Zhu","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.1073\/pnas.1120269109","article-title":"Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin","volume":"109","author":"Ambort","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15064","DOI":"10.1073\/pnas.0803124105","article-title":"The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria","volume":"105","author":"Johansson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.1073\/pnas.1006451107","article-title":"The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host\u2013microbial interactions","volume":"108","author":"Johansson","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1177\/41.10.8245407","article-title":"Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization","volume":"41","author":"Audie","year":"1993","journal-title":"J. Histochem. Cytochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1042\/bst0230800","article-title":"Human mucin genes: Genomic organization and expression of MUC4, MUC5AC and MUC5B","volume":"4","author":"Porchet","year":"1995","journal-title":"Biochem. Soc. Trans."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1165\/ajrcmb.17.5.2798","article-title":"Developmental expression of mucin genes in the human respiratory tract","volume":"17","author":"Reid","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1165\/ajrcmb.20.2.3259","article-title":"Developmental mucin gene expression in the human respiratory tract","volume":"20","author":"Buisine","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1016\/S0021-9258(17)41965-X","article-title":"Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor","volume":"269","author":"Gum","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1182\/blood-2012-01-405134","article-title":"Sequence and structure relationships within von Willebrand factor","volume":"120","author":"Zhou","year":"2012","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1042\/BST20170402","article-title":"Mucins: The frontline defence of the lung","volume":"46","author":"Ridley","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.critrevonc.2017.12.006","article-title":"Mucins: Structural diversity, biosynthesis, its role in pathogenesis and as possible therapeutic targets","volume":"122","author":"Dhanisha","year":"2018","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/joim.12910","article-title":"Mucus and mucins in diseases of the intestinal and respiratory tracts","volume":"285","author":"Hansson","year":"2019","journal-title":"J. Intern. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"31751","DOI":"10.1074\/jbc.274.45.31751","article-title":"The structure and assembly of secreted mucins","volume":"274","author":"Hill","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10288","DOI":"10.1021\/acs.jpcb.6b08109","article-title":"Preferred hydrogen-bonding partners of cysteine: Implications for regulating cys functions","volume":"120","author":"Mazmanian","year":"2016","journal-title":"J. Phys. Chem. B"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ympev.2009.03.035","article-title":"Mucin CYS domains are ancient and highly conserved modules that evolved in concert","volume":"52","author":"Desseyn","year":"2009","journal-title":"Mol. Phylogenetics Evol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1074\/mcp.M115.052993","article-title":"Reduced mucin-7 (Muc7) sialylation and altered saliva rheology in Sj\u00f6gren\u2019s syndrome associated oral dryness","volume":"15","author":"Chaudhury","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1023\/A:1006978818555","article-title":"Structural features of the human salivary mucin, MUC7","volume":"15","author":"Gururaja","year":"1998","journal-title":"Glycoconj. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1128\/AAC.47.2.643-652.2003","article-title":"MUC7 20-Mer: Investigation of antimicrobial activity, secondary structure, and possible mechanism of antifungal action","volume":"47","author":"Bobek","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/07391102.2000.10506654","article-title":"Solution structure of O-glycosylated C-terminal leucine zipper domain of human salivary mucin (MUC7)","volume":"18","author":"Narasimhamurthy","year":"2000","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Hakoshima, T. (2005). Leucine zippers. eLS (Encyclopedia of Life Sciences), John Wiley & Sons, Ltd.","DOI":"10.1038\/npg.els.0005049"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1177\/000348940411300812","article-title":"MUC8 mucin gene up-regulation in chronic rhinosinusitis","volume":"113","author":"Lee","year":"2004","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"L402","DOI":"10.1152\/ajplung.00210.2010","article-title":"Cystic fibrosis and the relationship between mucin and chloride secretion by cultures of human airway gland mucous cells","volume":"301","author":"Finkbeiner","year":"2011","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.freeradbiomed.2011.01.014","article-title":"Crosstalk between platelet-derived growth factor-induced Nox4 activation and MUC8 gene overexpression in human airway epithelial cells","volume":"50","author":"Kim","year":"2011","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1095\/biolreprod54.1.60","article-title":"Association of oviduct-specific glycoproteins with human and baboon (Papio anubis) ovarian oocytes and enhancement of human sperm binding to human hemizonae following in vitro incubation","volume":"54","author":"Mavrogianis","year":"1996","journal-title":"Biol. Reprod."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Allen, A., Bell, A., Mantle, M., and Pearson, J.P. (1982). The structure and physiology of gastrointestinal mucus. Mucus in Health and Disease\u2014II, Springer.","DOI":"10.1007\/978-1-4615-9254-9_15"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ejpb.2015.02.029","article-title":"The effect of nanoparticle permeation on the bulk rheological properties of mucus from the small intestine","volume":"96","author":"Wilcox","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.physiol.70.113006.100441","article-title":"Regulation of airway mucin gene expression","volume":"70","author":"Thai","year":"2008","journal-title":"Annu. Rev. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Rousseau, K., and Swallow, D.M. (2012). Mucin methods: Genes encoding mucins and their genetic variation with a focus on gel-forming mucins. Mucins, Humana Press.","DOI":"10.1007\/978-1-61779-513-8_1"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.3748\/wjg.v12.i37.6021","article-title":"Short mucin 6 alleles are associated with H pylori infection","volume":"12","author":"Nguyen","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15828","DOI":"10.1074\/jbc.274.22.15828","article-title":"Studies on the \u201cinsoluble\u201d glycoprotein complex from human colon. Identification of reduction-insensitive MUC2 oligomers and C-terminal cleavage","volume":"274","author":"Herrmann","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/mi.2016.45","article-title":"Core 1\u2013and 3\u2013derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice","volume":"10","author":"Bergstrom","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1042\/BST20160167","article-title":"How do they stick together? Bacterial adhesins implicated in the binding of bacteria to the human gastrointestinal mucins","volume":"45","author":"Kalach","year":"2017","journal-title":"Biochem. Soc. Trans."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"31371","DOI":"10.1074\/jbc.M802814200","article-title":"Prointerleukin-18 is activated by meprin \u03b2 in vitro and in vivo in intestinal inflammation","volume":"283","author":"Banerjee","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"47248","DOI":"10.1074\/jbc.M208483200","article-title":"The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment","volume":"277","author":"Godl","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/rr82","article-title":"\u2018CFTR-opathies\u2019: Disease phenotypes associated with cystic fibrosis transmembrane regulator gene mutations","volume":"2","author":"Noone","year":"2001","journal-title":"Respir. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00535-018-1509-4","article-title":"The role of small intestinal bacterial overgrowth in cystic fibrosis: A randomized case-controlled clinical trial with rifaximin","volume":"54","author":"Furnari","year":"2019","journal-title":"J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1016\/j.jcf.2017.07.006","article-title":"Gallbladder and bile duct disease in cystic fibrosis","volume":"16","author":"Assis","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jcf.2008.10.004","article-title":"Mechanism of direct bicarbonate transport by the CFTR anion channel","volume":"8","author":"Tang","year":"2009","journal-title":"J. Cyst. Fibros."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/ncb0404-292","article-title":"Bicarbonate secretion: It takes two to tango","volume":"6","author":"Gray","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"C1057","DOI":"10.1152\/ajpcell.00454.2009","article-title":"The switch of intestinal Slc26 exchangers from anion absorptive to HCO3\u2212 secretory mode is dependent on CFTR anion channel function","volume":"298","author":"Singh","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0140-6736(08)61162-9","article-title":"Cystic fibrosis: Impaired bicarbonate secretion and mucoviscidosis","volume":"372","author":"Quinton","year":"2008","journal-title":"Lancet"},{"key":"ref_84","unstructured":"George, T., and Brady, M.F. (2024). Ethylenediaminetetraacetic Acid (EDTA). StatPearls, StatPearls Publishing LLC."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12396","DOI":"10.1073\/pnas.1407597111","article-title":"Microbial-induced meprin \u03b2 cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus","volume":"111","author":"Ermund","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.mam.2008.08.002","article-title":"Meprins, membrane-bound and secreted astacin metalloproteinases","volume":"29","author":"Sterchi","year":"2008","journal-title":"Mol. Asp. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1046\/j.1432-1327.1999.00071.x","article-title":"Secretion of human meprin from intestinal epithelial cells depends on differential expression of the \u03b1 and \u03b2 subunits","volume":"259","author":"Lottaz","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"28126","DOI":"10.1074\/jbc.272.44.28126","article-title":"Activation mechanism of meprins, members of the astacin metalloendopeptidase family","volume":"272","author":"Johnson","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"G273","DOI":"10.1152\/ajpgi.00504.2009","article-title":"Balance of meprin A and B in mice affects the progression of experimental inflammatory bowel disease","volume":"300","author":"Banerjee","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1042\/bj20031163","article-title":"Human meprin alpha and beta homo-oligomers: Cleavage of basement membrane proteins and sensitivity to metalloprotease inhibitors","volume":"378","author":"Kruse","year":"2004","journal-title":"Biochem. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"M111.009233","DOI":"10.1074\/mcp.M111.009233","article-title":"Proteomic analyses reveal an acidic prime side specificity for the astacin metalloprotease family reflected by physiological substrates","volume":"10","author":"Schilling","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"13308","DOI":"10.1074\/jbc.M114.559088","article-title":"ADAM10 is the major sheddase responsible for the release of membrane-associated meprin A","volume":"289","author":"Herzog","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nm0102-41","article-title":"Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells","volume":"8","author":"Lemjabbar","year":"2002","journal-title":"Nat. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1016\/j.bbamcr.2017.07.011","article-title":"Role of ADAM10 in intestinal crypt homeostasis and tumorigenesis","volume":"1864","author":"Dempsey","year":"2017","journal-title":"Biochim. Et Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00018-012-1106-2","article-title":"The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin \u03b2 and ADAM10","volume":"70","author":"Jefferson","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1016\/j.celrep.2017.10.087","article-title":"Mucus detachment by host metalloprotease meprin \u03b2 requires shedding of its inactive pro-form, which is abrogated by the pathogenic protease RgpB","volume":"21","author":"Wichert","year":"2017","journal-title":"Cell Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1042\/BJ20141417","article-title":"Metalloprotease meprin \u03b2 is activated by transmembrane serine protease matriptase-2 at the cell surface thereby enhancing APP shedding","volume":"470","author":"Schmidt","year":"2015","journal-title":"Biochem. J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"G922","DOI":"10.1152\/ajpgi.2001.280.5.G922","article-title":"The adherent gastrointestinal mucus gel layer: Thickness and physical state in vivo","volume":"280","author":"Atuma","year":"2001","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1172\/JCI116966","article-title":"Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ hybridization","volume":"93","author":"Strong","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"17350","DOI":"10.1038\/s41598-019-53768-0","article-title":"The MUC5B mucin polymer is dominated by repeating structural motifs and its topology is regulated by calcium and pH","volume":"9","author":"Hughes","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"18857","DOI":"10.1074\/jbc.273.30.18857","article-title":"Dimerization of the human MUC2 mucin in the endoplasmic reticulum is followed by a N-glycosylation-dependent transfer of the mono- and dimers to the Golgi apparatus","volume":"273","author":"Asker","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jbiotec.2012.06.038","article-title":"Differences in the glycosylation of recombinant proteins expressed in HEK and CHO cells","volume":"161","author":"Croset","year":"2012","journal-title":"J. Biotechnol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.4049\/jimmunol.1901145","article-title":"Choice of Host Cell Line Is Essential for the Functional Glycosylation of the Fc Region of Human IgG1 Inhibitors of Influenza B Viruses","volume":"204","author":"Blundell","year":"2020","journal-title":"J. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"B\u00f6hm, E., Seyfried, B.K., Dockal, M., Graninger, M., Hasslacher, M., Neurath, M., Konetschny, C., Matthiessen, P., Mitterer, A., and Scheiflinger, F. (2015). Differences in N-glycosylation of recombinant human coagulation factor VII derived from BHK, CHO, and HEK293 cells. BMC Biotechnol., 15.","DOI":"10.1186\/s12896-015-0205-1"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Ermund, A., Gustafsson, J.K., Hansson, G.C., and Keita, \u00c5.V. (2013). Mucus properties and goblet cell quantification in mouse, rat and human ileal Peyer\u2019s patches. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083688"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s00018-002-8412-z","article-title":"The multifaceted Paneth cell","volume":"59","author":"Porter","year":"2002","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/1471-230X-14-93","article-title":"Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children","volume":"14","author":"Simmonds","year":"2014","journal-title":"BMC Gastroenterol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.3748\/wjg.v16.i24.2978","article-title":"Small intestinal bacterial overgrowth syndrome","volume":"16","author":"Bures","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3164\/jcbn.09-77","article-title":"Peyer\u2019s patches in the terminal ileum in ulcerative colitis: Magnifying endoscopic findings","volume":"46","author":"Ishii","year":"2010","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1042\/cs0950097","article-title":"A novel method for the visualization of the in situ mucus layer in rat and man","volume":"95","author":"Jordan","year":"1998","journal-title":"Clin. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"19.12.1","DOI":"10.1002\/0471143030.cb1912s44","article-title":"Overview: Generation of gene knockout mice","volume":"44","author":"Hall","year":"2009","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"8403","DOI":"10.1073\/pnas.111009698","article-title":"Manipulating the mammalian genome by homologous recombination","volume":"98","author":"Vasquez","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Krych, L., Hansen, C.H.F., Hansen, A.K., van den Berg, F.W.J., and Nielsen, D.S. (2013). Quantitatively Different, yet Qualitatively Alike: A Meta-Analysis of the Mouse Core Gut Microbiome with a View towards the Human Gut Microbiome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062578"}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/16\/12\/1663\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:57:29Z","timestamp":1760108249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/16\/12\/1663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,12]]},"references-count":113,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["polym16121663"],"URL":"https:\/\/doi.org\/10.3390\/polym16121663","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,12]]}}}