基于蛋白质组学的肝纤维化大鼠血清对肝星状细胞的作用靶点及信号通路研究

肝脏 ›› 2021, Vol. 26 ›› Issue (7): 737-741.

基于蛋白质组学的肝纤维化大鼠血清对肝星状细胞的作用靶点及信号通路研究

黎敏航, 蔡碧莲, 蒋云霞, 罗伟生

530001 南宁广西中医药大学

收稿日期:2020-08-19 出版日期:2021-07-31 发布日期:2021-09-02
通讯作者: 罗伟生,Email:4011188@qq.com
基金资助:
国家自然科学基金资助项目(81660079)

A proteomics study on the mechanism and signaling pathways for the activation of hepatic stellate cells by serum from liver fibrotic rats

LI Min-hang, CAI Bi-lian, JIANG Yun-xia, LUO Wei-sheng

Guangxi University of Chinese Medicine, Nanning 530001, China

Received:2020-08-19 Online:2021-07-31 Published:2021-09-02
Contact: LUO Wei-sheng,Email:4011188@qq.com

摘要/Abstract

摘要： 目的研究体外的大鼠肝星状细胞(HSC)被纤维化大鼠血清激活的可能机制。方法分别使用纤维化大鼠血清以及正常大鼠血清干预HSC 14 d后,提取两组HSC的全蛋白,使用label free的方法对其进行蛋白质组学分析,采用非数据依赖型的采集方法,比较得出差异蛋白,使用基因本体(gene ontology,GO)数据库、京都基因和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)数据库对差异蛋白进行分析。结果两种方法共鉴定出差异蛋白221个,这些蛋白主要定位在细胞器与膜上,能够执行催化活性和细胞功能调节等分子功能,它们参与代谢、生物调节等26种生物过程。KEGG富集分析发现这些蛋白质主要参与了类固醇与胆固醇代谢的过程。结论钙粘蛋白-2、纤维连接蛋白、Notch 1蛋白和Notch 2蛋白异常表达时,与HSC的激活高度相关,这几种蛋白可能是HSC激活的靶点蛋白;细胞外基质相互作用信号通路以及Notch信号通路是与HSC激活高度相关的通路。

关键词: 大鼠, 肝星状细胞, 肝纤维化机制, 蛋白质组学

Abstract: Objective To study on the possible mechanism for the activation of hepatic stellate cells (HSCs) by serum from liver fibrotic rats in vitro. Methods Whole proteins of HSCs were extracted after 14 days incubation of the cells with serum from fibrotic or normal rats. The proteins were then analyzed by a label free method. The differentially expressed proteins were analyzed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)databases. Results A total of 221 differential proteins were identified between two cellular preparations. These proteins were mainly located in Organelles and membranes, and could perform molecular functions such as catalytic activity and cellular function regulation. They were involved in 26 biological processes such as metabolism and biological regulation. KEGG enrichment analysis showed that these proteins were mainly involved in steroid and cholesterol metabolisms. Conclusion The abnormal expressions of cadherin-2, fibronectin, Notch 1 and Notch 2 proteins are highly correlated with the activation of HSC. These results suggest that these proteins may be the targets of HSC activation, and that the extracellular matrix and Notch signaling pathways are highly correlated with HSC activation.

Key words: Hepatic stellate cells, Proteomics, Mechanism of liver fibrosis, Rat

黎敏航, 蔡碧莲, 蒋云霞, 罗伟生. 基于蛋白质组学的肝纤维化大鼠血清对肝星状细胞的作用靶点及信号通路研究[J]. 肝脏, 2021, 26(7): 737-741.

LI Min-hang, CAI Bi-lian, JIANG Yun-xia, LUO Wei-sheng. A proteomics study on the mechanism and signaling pathways for the activation of hepatic stellate cells by serum from liver fibrotic rats[J]. Chinese Hepatolgy, 2021, 26(7): 737-741.

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