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Mucin Glycan Expression is Individual-Specific and Governed by the In Situ Microenvironment

机译:粘蛋白聚糖表达是特定于个体的,并受原位微环境控制。

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Mucin glycosylation and individual susceptibility to disease is linked to the In Situ microenvironment that determines features of the individual- and disease-specific glycans. In tissue culture paradigm, the In Situ environment is not recreated and the synthesis of signature glycans vanishes. To evaluate the impact of the in situ-specific gastric epithelial environment on mucin glycan synthesis we investigated gastric mucin collected from 36 individual rats subjected to the same conditions and diet. The secretion collected during 3 hours of gastric perfusion contained from 67.7 to 1096.6 nmol mucin glycans and from 42.0 to 245.8 nmol glycosphingolipids (GSL). We identified four groups, each consisting of 6 animals, that contained O-glycans interacting with apical epithelial mucin receptor comprised of N-acetylgalactosamine (GalNAc), galactose (Gal), N-acetylglucosamine (GlcNAc) and fucose (Fuc) in the ratio of 1:2:2:1, 1:2:3:1, 1:3:2:1, and 1:4:2:1. The remaining 10 rats produced glycans containing GalNAc, Gal, GlcNAc, Fuc in ratio 1:1:1:1, partially fucosylated glycans, and Fuc-free glycans consisting of GalNAc:Gal:GlcNAc in ratio of 1:4:2. The data support our hypothesis that individual-specific-gastric epithelial environment and individual-specific metabolome provide final imprint on the quantity, composition, and termination of mucin O-glycans.
机译:粘蛋白糖基化和对疾病的易感性与决定个体和疾病特异性聚糖特征的原位微环境有关。在组织培养范式中,不会重新创建原位环境,并且标记聚糖的合成消失。为了评估原位特异性胃上皮环境对粘蛋白聚糖合成的影响,我们调查了从36只在相同条件和饮食条件下的大鼠收集的胃粘蛋白。胃灌注3小时期间收集到的分泌物包含67.7至1096.6 nmol粘蛋白聚糖和42.0至245.8 nmol糖鞘脂(GSL)。我们确定了四组,每组由6只动物组成,它们包含与N-乙酰半乳糖胺(GalNAc),半乳糖(Gal),N-乙酰氨基葡糖胺(GlcNAc)和岩藻糖(Fuc)组成的顶端上皮粘蛋白受体相互作用的O-聚糖1:2:2:1、1:2:3:1、1:3:2:1和1:4:2:1。其余10只大鼠产生的聚糖含有比例为1:1:1:1的GalNAc,Gal,GlcNAc,Fuc,部分岩藻糖基化的聚糖和由比例为1:4:2的由GalNAc:Gal:GlcNAc组成的无Fuc的聚糖。数据支持我们的假设,即个体特异性胃上皮环境和个体特异性代谢组在粘蛋白O聚糖的数量,组成和终止上提供了最终烙印。

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