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COL1A1 作为 2 型糖尿病潜在的新生物标志物和治疗靶点。

COL1A1 as a potential new biomarker and therapeutic target for type 2 diabetes.

机构信息

Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

出版信息

Pharmacol Res. 2021 Mar;165:105436. doi: 10.1016/j.phrs.2021.105436. Epub 2021 Jan 23.

Abstract

Type 2 diabetes (T2D) is a public health problem with a rising incidence worldwide. In this study, a potential new biomarker for T2D and mechanisms underlying the hypoglycemic effects of Enteromorpha prolifera oligosaccharide were investigated. Tandem mass tag labeling with LC-MS/MS was used to identify the differentially expressed proteins (DEPs) between the jejunum of diabetic rats and control rats. Correlations between glycometabolic parameters and DEPs were revealed by a network analysis. The expression levels of target genes in key metabolic pathways were further evaluated to identify candidate biomarkers. Among 6810 total proteins, approximately 88 % were quantified, of which 148 DEPs with a fold change of <0.83 or>1.2 and a corrected p-value of <0.05 were identified. A KEGG enrichment analysis indicated that the hypoglycaemic effects of E. prolifera oligosaccharide involved the PI3K/AKT and extracellular matrix receptor interaction signaling pathways. More importantly, Col1a1 was the most significant gene in the extracellular matrix receptor interaction pathway and was linked to hypoglycaemic activity for the first time. Thus, Col1a1 is a novel potential therapeutic target for alleviating T2D.

摘要

2 型糖尿病(T2D)是一种全球发病率不断上升的公共卫生问题。本研究旨在探讨 T2D 的潜在新生物标志物以及浒苔低聚糖降血糖作用的潜在机制。采用 LC-MS/MS 的串联质量标签标记法鉴定了糖尿病大鼠和对照组大鼠空肠之间差异表达的蛋白质(DEPs)。通过网络分析揭示了糖代谢参数与 DEPs 之间的相关性。进一步评估关键代谢途径中的靶基因表达水平,以鉴定候选生物标志物。在 6810 种总蛋白中,约有 88%被定量,其中鉴定出 148 种具有<0.83 或>1.2 倍折叠变化和校正 p 值<0.05 的差异表达蛋白。KEGG 富集分析表明,浒苔低聚糖的降血糖作用涉及 PI3K/AKT 和细胞外基质受体相互作用信号通路。更重要的是,Col1a1 是细胞外基质受体相互作用通路中最重要的基因,这是首次将其与降血糖活性联系起来。因此,Col1a1 是一种缓解 T2D 的新型潜在治疗靶点。

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