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分析肝纤维化小鼠中糖相关基因表达和糖谱。

Analysis of glycan-related genes expression and glycan profiles in mice with liver fibrosis.

机构信息

Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an 710069, China.

出版信息

J Proteome Res. 2012 Nov 2;11(11):5277-85. doi: 10.1021/pr300484j. Epub 2012 Oct 17.

Abstract

Protein glycosylation plays an important role in the pathogenesis and progression of various liver diseases. However, little is known about the precise alterations in protein glycosylation or the potential correlation between glycan-related genes expression and glycan profiles in liver fibrosis. The aim of the study was to investigate potential associations between glycan-related genes expression and glycan profiles to evaluate liver fibrosis in a mouse model. Analyses of glycan-related genes expression and glycan profiles were performed using oligonucleotide microarrays and lectin microarrays, respectively. Real-time PCR and Western blot were used to confirm any altered glycan-related genes expression levels and protein levels. Moreover, altered glycan patterns on the surface of hepatocytes were verified by lectin histochemistry. These results revealed that the mRNA levels of 10 glycan-related genes were significantly altered in fibrotic liver. Furthermore, we observed an increase in multivalent sialic acid, poly-LacNAc, sialyl-T-antigen, Fucoseα-1,3/6GlcNAc, and GalNAcα1-3Gal in fibrotic liver specimens, whereas GlcNAc oligomers was decreased in fibrotic liver. Our findings indicated that the synthetic pathway of "Tn antigen → T antigen (core-1) → sialyl-T antigen" was activated for O-glycan during the process of liver fibrosis.

摘要

蛋白质糖基化在各种肝脏疾病的发病机制和进展中起着重要作用。然而,对于糖基化蛋白质的精确改变,或者糖基化相关基因表达与肝纤维化中糖谱之间的潜在相关性,人们知之甚少。本研究旨在探讨糖基化相关基因表达与糖谱之间的潜在关联,以评估小鼠模型中的肝纤维化。使用寡核苷酸微阵列和凝集素微阵列分别进行糖基化相关基因表达和糖谱分析。实时 PCR 和 Western blot 用于确认任何改变的糖基化相关基因表达水平和蛋白水平。此外,通过凝集素组织化学验证肝细胞表面改变的糖模式。这些结果表明,10 个糖基化相关基因的 mRNA 水平在纤维化肝脏中明显改变。此外,我们观察到纤维化肝组织中多价唾液酸、多聚-LacNAc、唾液酸-T 抗原、岩藻糖α-1,3/6GlcNAc 和 GalNAcα1-3Gal 增加,而纤维化肝中 GlcNAc 低聚物减少。我们的研究结果表明,在肝纤维化过程中,O-聚糖的“Tn 抗原→T 抗原(核心 1)→唾液酸-T 抗原”合成途径被激活。

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