Zinc Deficiency Disturbs Mucin Expression, ...
Document type :
Article dans une revue scientifique
DOI :
Permalink :
Title :
Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells
Author(s) :
Maares, Maria [Auteur]
Technical University of Berlin / Technische Universität Berlin [TU]
Keil, Claudia [Auteur]
Technical University of Berlin / Technische Universität Berlin [TU]
Straubing, Sophia [Auteur]
Technical University of Berlin / Technische Universität Berlin [TU]
Masselot, Catherine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Haase, Hajo [Auteur]
Technical University of Berlin / Technische Universität Berlin [TU]
Technical University of Berlin / Technische Universität Berlin [TU]
Keil, Claudia [Auteur]
Technical University of Berlin / Technische Universität Berlin [TU]
Straubing, Sophia [Auteur]
Technical University of Berlin / Technische Universität Berlin [TU]
Masselot, Catherine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Haase, Hajo [Auteur]
Technical University of Berlin / Technische Universität Berlin [TU]
Journal title :
International Journal of Molecular Sciences
Abbreviated title :
IJMS
Volume number :
21
Pages :
6149
Publisher :
MDPI AG
Publication date :
2020-08-26
ISSN :
1422-0067
English keyword(s) :
zinc deficiency
intestinal mucins
O-glycosylation
goblet cells
MUC2
MUC5AC
zinc homeostasis
glycosyltransferases
C1GALT1
B3GNT6
intestinal mucins
O-glycosylation
goblet cells
MUC2
MUC5AC
zinc homeostasis
glycosyltransferases
C1GALT1
B3GNT6
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Approximately 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 ...
Show more >Approximately 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.Show less >
Show more >Approximately 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.Show less >
Language :
Anglais
Audience :
Non spécifiée
Administrative institution(s) :
Université de Lille
CNRS
CNRS
Research team(s) :
Génétique des enveloppes bactériennes
Submission date :
2021-03-23T14:09:01Z
2021-03-24T07:00:45Z
2021-03-24T07:00:45Z
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