Technische Universität Berlin, Chair of Food Chemistry and Toxicology, Straße des 17. Juni 135, 10623 Berlin, Germany.
Unité de Glycobiologie Structurale et Fonctionnelle, University of Lille, CNRS, UMR8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, F59000 Lille, France.
Int J Mol Sci. 2020 Aug 26;21(17):6149. doi: 10.3390/ijms21176149.
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 , , and 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 and mRNA expression with ongoing cell differentiation. A lack of zinc perturbed mucin synthesis predominantly on the post-translational level, as ZD cells produced shorter -glycans and the main -glycan pattern was shifted in favor of core-3-based mucins. The expression of glycosyltransferases that determine the formation of core 1-4 -glycans was altered in zinc deficiency. In particular, mRNA catalyzing core 3 formation was elevated and and 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.
全世界约有 10 亿人患有锌缺乏症，这对他们的健康造成了严重的影响，如严重损害肠道健康。除了肠道上皮细胞极度退化外，缺锌（ZD）动物的肠道黏液也受到严重干扰。然而，锌缺乏对肠道黏液产生的杯状细胞的细胞过程以及对锌的重要性仍然未知。为此，本研究使用体外杯状细胞模型 HT-29-MTX 研究了锌缺乏对肠道黏液的合成、产生和分泌以及对杯状细胞锌稳态的影响。锌剥夺降低了它们的细胞内锌含量，改变了肠道锌转运体 、 和 的表达，并增加了它们的锌吸收能力，概述了杯状细胞锌稳态的调节机制。在缺锌时，黏液的合成和分泌受到严重干扰，影响了 和 mRNA 的表达，并伴随着细胞分化的进行。缺锌会干扰黏液的合成，主要是在翻译后水平上，因为 ZD 细胞产生的 -糖链较短，主要的 -糖链模式向核心 3 基黏液倾斜。决定核心 1-4 -糖链形成的糖基转移酶的表达在缺锌时发生改变。特别是，催化核心 3 形成的 mRNA 上调，而在 ZD 细胞中延长核心 1 的 和 下调。这些关于锌缺乏症损害肠道黏液稳定性的分子机制的新见解表明了锌对于这种物理屏障的形成和维持的必要性。
