Vanhooren Valerie, Vandenbroucke Roosmarijn E, Dewaele Sylviane, Van Hamme Evelien, Haigh Jody J, Hochepied Tino, Libert Claude
Department for Molecular Biomedical Research, VIB, Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
PLoS One. 2013 Dec 5;8(12):e79883. doi: 10.1371/journal.pone.0079883. eCollection 2013.
Glycosylation is an essential post-translational modification, which determines the function of proteins and important processes such as inflammation. β-1,4-galactosyltransferase I (βGalT1) is a key enzyme involved in the addition of galactose moieties to glycoproteins. Intestinal mucins are glycoproteins that protect the gut barrier against invading pathogens and determine the composition of the intestinal microbiota. Proper glycosylation of mucus is important in this regard. By using ubiquitously expressing βGalT1 transgenic mice, we found that this enzyme led to strong galactosylation of mucus proteins, isolated from the gut of mice. This galactosylation was associated with a drastic change in composition of gut microbiota, as TG mice had a significantly higher Firmicutes to Bacteroidetes ratio. TG mice were strongly protected against TNF-induced systemic inflammation and lethality. Moreover, βGalT1 transgenic mice were protected in a model of DSS-induced colitis, at the level of clinical score, loss of body weight, colon length and gut permeability. These studies put βGalT1 forward as an essential protective player in exacerbated intestinal inflammation. Optimal galactosylation of N-glycans of mucus proteins, determining the bacterial composition of the gut, is a likely mechanism of this function.
糖基化是一种重要的翻译后修饰，它决定蛋白质的功能以及诸如炎症等重要过程。β-1,4-半乳糖基转移酶I（βGalT1）是一种关键酶，参与将半乳糖部分添加到糖蛋白中。肠道黏蛋白是糖蛋白，可保护肠道屏障免受入侵病原体的侵害，并决定肠道微生物群的组成。在这方面，黏液的适当糖基化很重要。通过使用广泛表达βGalT1的转基因小鼠，我们发现该酶导致从小鼠肠道分离的黏液蛋白发生强烈的半乳糖基化。这种半乳糖基化与肠道微生物群组成的剧烈变化有关，因为转基因小鼠的厚壁菌门与拟杆菌门的比例明显更高。转基因小鼠对肿瘤坏死因子诱导的全身炎症和致死性具有很强的抵抗力。此外，在临床评分、体重减轻、结肠长度和肠道通透性方面，βGalT1转基因小鼠在右旋糖酐硫酸钠诱导的结肠炎模型中受到保护。这些研究表明βGalT1是加剧肠道炎症中重要的保护因子。黏液蛋白N-聚糖的最佳半乳糖基化决定了肠道的细菌组成，这可能是其发挥该功能的机制。
