{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:50:48Z","timestamp":1793645448539,"version":"4.5.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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 <jats:italic>MUC2 KO<\/jats:italic> 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 <jats:italic>MUC2 KO<\/jats:italic>, 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 <jats:italic>Muc2<jats:sup>+\/+<\/jats:sup><\/jats:italic> but not <jats:italic>Muc2<jats:sup>-\/-<\/jats:sup><\/jats:italic> littermates, were accompanied by a rapid increase in <jats:italic>Fcgbp<\/jats:italic> 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.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1211336","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T05:56:45Z","timestamp":1686203805000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["IgGFc-binding protein and MUC2 mucin produced by colonic goblet-like cells spatially interact non-covalently and regulate wound healing"],"prefix":"10.3389","volume":"14","author":[{"given":"Hayley","family":"Gorman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"France","family":"Moreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Dufour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"Chadee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e982426","DOI":"10.4161\/21688370.2014.982426","article-title":"Roles and regulation of the mucus barrier in the gut","volume":"3","author":"Cornick","year":"2015","journal-title":"Tissue Barriers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1462-5822.2001.00090.x","article-title":"The gastrointestinal ecosystem: a precarious alliance among epithelium, immunity and microbiota: microreview","volume":"3","author":"McCracken","year":"2001","journal-title":"Cell Microbiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.02.010","article-title":"The densely O-glycosylated MUC2 mucin protects the intestine and provides food for the commensal bacteria","volume":"428","author":"Arike","year":"2016","journal-title":"J Mol Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-010-0131-2","article-title":"Intestinal goblet cells and mucins in health and disease: recent insights and progress","volume":"12","author":"Kim","year":"2010","journal-title":"Curr Gastroenterol Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.88","article-title":"Immunological aspects of intestinal mucus and mucins","volume":"16","author":"Johansson","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B7","doi-asserted-by":"publisher","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"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1159\/000163037","article-title":"Role of intestinal mucins in innate host defense mechanisms against pathogens","volume":"1","author":"Dharmani","year":"2009","journal-title":"J Innate Immun"},{"key":"B9","first-page":"57","article-title":"Production, structure and function of gastrointestinal mucins","volume-title":"Infections of the gastrointestinal tract","author":"Moncada","year":"2002"},{"key":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00047.2013","article-title":"Studies of mucus in mouse stomach, small intestine, and colon. 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