Zinc Deficiency Disturbs Mucin Expression, <i>O</i>-Glycosylation and Secretion by Intestinal Goblet Cells
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)...
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/17/6149 |
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| author | Maria Maares Claudia Keil Sophia Straubing Catherine Robbe-Masselot Hajo Haase |
| author_facet | Maria Maares Claudia Keil Sophia Straubing Catherine Robbe-Masselot Hajo Haase |
| author_sort | Maria Maares |
| collection | DOAJ |
| description | 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 <i>ZIP-4</i>, <i>ZIP-5</i>, and <i>ZnT1</i> 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 <i>MUC2</i> and <i>MUC5AC</i> mRNA expression with ongoing cell differentiation. A lack of zinc perturbed mucin synthesis predominantly on the post-translational level, as ZD cells produced shorter <i>O</i>-glycans and the main <i>O</i>-glycan pattern was shifted in favor of core-3-based mucins. The expression of glycosyltransferases that determine the formation of core 1-4 <i>O</i>-glycans was altered in zinc deficiency. In particular, <i>B3GNT6</i> mRNA catalyzing core 3 formation was elevated and <i>C2GNT1</i> and <i>C2GNT3</i> 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. |
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| spelling | doaj.art-c22c0e7a7fa649ec80a461081d3543a42023-11-20T11:26:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117614910.3390/ijms21176149Zinc Deficiency Disturbs Mucin Expression, <i>O</i>-Glycosylation and Secretion by Intestinal Goblet CellsMaria Maares0Claudia Keil1Sophia Straubing2Catherine Robbe-Masselot3Hajo Haase4Technische Universität Berlin, Chair of Food Chemistry and Toxicology, Straße des 17. Juni 135, 10623 Berlin, GermanyTechnische Universität Berlin, Chair of Food Chemistry and Toxicology, Straße des 17. Juni 135, 10623 Berlin, GermanyTechnische Universität Berlin, Chair of Food Chemistry and Toxicology, Straße des 17. Juni 135, 10623 Berlin, GermanyUnité de Glycobiologie Structurale et Fonctionnelle, University of Lille, CNRS, UMR8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F59000 Lille, FranceTechnische Universität Berlin, Chair of Food Chemistry and Toxicology, Straße des 17. Juni 135, 10623 Berlin, GermanyApproximately 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 <i>ZIP-4</i>, <i>ZIP-5</i>, and <i>ZnT1</i> 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 <i>MUC2</i> and <i>MUC5AC</i> mRNA expression with ongoing cell differentiation. A lack of zinc perturbed mucin synthesis predominantly on the post-translational level, as ZD cells produced shorter <i>O</i>-glycans and the main <i>O</i>-glycan pattern was shifted in favor of core-3-based mucins. The expression of glycosyltransferases that determine the formation of core 1-4 <i>O</i>-glycans was altered in zinc deficiency. In particular, <i>B3GNT6</i> mRNA catalyzing core 3 formation was elevated and <i>C2GNT1</i> and <i>C2GNT3</i> 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.https://www.mdpi.com/1422-0067/21/17/6149zinc deficiencyintestinal mucins<i>O</i>-glycosylationgoblet cellsMUC2MUC5AC |
| spellingShingle | Maria Maares Claudia Keil Sophia Straubing Catherine Robbe-Masselot Hajo Haase Zinc Deficiency Disturbs Mucin Expression, <i>O</i>-Glycosylation and Secretion by Intestinal Goblet Cells International Journal of Molecular Sciences zinc deficiency intestinal mucins <i>O</i>-glycosylation goblet cells MUC2 MUC5AC |
| title | Zinc Deficiency Disturbs Mucin Expression, <i>O</i>-Glycosylation and Secretion by Intestinal Goblet Cells |
| title_full | Zinc Deficiency Disturbs Mucin Expression, <i>O</i>-Glycosylation and Secretion by Intestinal Goblet Cells |
| title_fullStr | Zinc Deficiency Disturbs Mucin Expression, <i>O</i>-Glycosylation and Secretion by Intestinal Goblet Cells |
| title_full_unstemmed | Zinc Deficiency Disturbs Mucin Expression, <i>O</i>-Glycosylation and Secretion by Intestinal Goblet Cells |
| title_short | Zinc Deficiency Disturbs Mucin Expression, <i>O</i>-Glycosylation and Secretion by Intestinal Goblet Cells |
| title_sort | zinc deficiency disturbs mucin expression i o i glycosylation and secretion by intestinal goblet cells |
| topic | zinc deficiency intestinal mucins <i>O</i>-glycosylation goblet cells MUC2 MUC5AC |
| url | https://www.mdpi.com/1422-0067/21/17/6149 |
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