Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells

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dc.contributor.authorMaares, Maria
dc.contributor.authorKeil, Claudia
dc.contributor.authorStraubing, Sophia
dc.contributor.authorRobbe-Masselot, Catherine
dc.contributor.authorHaase, Hajo
dc.date.accessioned2022-09-12T08:52:52Z
dc.date.available2022-09-12T08:52:52Z
dc.date.issued2020-08-26
dc.date.updated2022-09-05T20:10:55Z
dc.description.abstractApproximately 1 billion people worldwide suffer from zinc deficiency, with severe consequences for their well-being, such as critically impaired intestinal health. In addition to an extreme degeneration of the intestinal epithelium, the intestinal mucus is seriously disturbed in zinc-deficient (ZD) animals. The underlying cellular processes as well as the relevance of zinc for the mucin-producing goblet cells, however, remain unknown. To this end, this study examines the impact of zinc deficiency on the synthesis, production, and secretion of intestinal mucins as well as on the zinc homeostasis of goblet cells using the in vitro goblet cell model HT-29-MTX. Zinc deprivation reduced their cellular zinc content, changed expression of the intestinal zinc transporters ZIP-4, ZIP-5, and ZnT1 and increased their zinc absorption ability, outlining the regulatory mechanisms of zinc homeostasis in goblet cells. Synthesis and secretion of mucins were severely disturbed during zinc deficiency, affecting both MUC2 and MUC5AC mRNA expression with ongoing cell differentiation. A lack of zinc perturbed mucin synthesis predominantly on the post-translational level, as ZD cells produced shorter O-glycans and the main O-glycan pattern was shifted in favor of core-3-based mucins. The expression of glycosyltransferases that determine the formation of core 1-4 O-glycans was altered in zinc deficiency. In particular, B3GNT6 mRNA catalyzing core 3 formation was elevated and C2GNT1 and C2GNT3 elongating core 1 were downregulated in ZD cells. These novel insights into the molecular mechanisms impairing intestinal mucus stability during zinc deficiency demonstrate the essentiality of zinc for the formation and maintenance of this physical barrier.en
dc.description.sponsorshipDFG, 316442145, FOR 2558: Interaktionen von essenziellen Spurenelementen in gesunden und erkrankten älteren Menschen(TraceAge)en
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/17413
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-16194
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftende
dc.subject.otherzinc deficiencyen
dc.subject.otherintestinal mucinsen
dc.subject.otherO-glycosylationen
dc.subject.othergoblet cellsen
dc.subject.otherMUC2en
dc.subject.otherMUC5ACen
dc.subject.otherzinc homeostasisen
dc.subject.otherglycosyltransferasesen
dc.subject.otherC1GALT1en
dc.subject.otherB3GNT6en
dc.titleZinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cellsen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber6149en
dcterms.bibliographicCitation.doi10.3390/ijms21176149en
dcterms.bibliographicCitation.issue17en
dcterms.bibliographicCitation.journaltitleInternational Journal of Molecular Sciencesen
dcterms.bibliographicCitation.originalpublishernameMDPIen
dcterms.bibliographicCitation.originalpublisherplaceBaselen
dcterms.bibliographicCitation.volume21en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Lebensmitteltechnologie und Lebensmittelchemie::FG Lebensmittelchemie und Toxikologiede
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Lebensmittelchemie und Toxikologiede
tub.affiliation.instituteInst. Lebensmitteltechnologie und Lebensmittelchemiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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