The protective effects of phosphoserine aminotransferase 1 (PSAT1) against hepatic ischemia–reperfusion injury

IF 3.6 3区 生物学 Q3 CELL BIOLOGY
Yinzhi Deng, Hesheng Luo
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Abstract

Hepatic ischemia–reperfusion (I/R) injury is a severe clinical syndrome, causing a profound medical and socioeconomic burden worldwide. This study aimed to explore underlying biomarkers and treatment targets in the progression of hepatic I/R injury. We screened gene expression profiles of the hepatic I/R injury from the Gene Expression Omnibus (GEO) database, downloaded expression profiles data (GSE117066). Differentially expressed genes (DEGs) were identified through cluster of the PPI network, and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The bioinformatics analysis was used to identify biomarkers that alleviate hepatic I/R injury. Finally, the effects of hub gene were investigated by in vitro and in vivo experiments. A total of 162 DEGs (76 up-regulated and 86 down-regulated genes) were extracted between sham and I/R, and 248 DEGs (118 up-regulated and 130 down-regulated genes) were extracted between I/R and ischemic postconditioning (IPO). The cluster of the PPI network and maximal clique centrality (MCC) method of the common DEGs were performed to identify the phosphoserine aminotransferase 1 (PSAT1) as the potential gene for hepatic I/R injury. Then, the H-E, TUNEL and PCNA staining were indicated that the hepatic injury score was highest in I/R 6 h. The expression level of apoptosis-related proteins was consistent with the pathological results. Both gain- and loss-of-function assays demonstrated that hepatic I/R injury was alleviated by PSAT1. PSAT1 may play crucial roles in hepatic I/R injury and thus serves as a hub biomarker for hepatic I/R injury prognosis and individual-based treatment.

Abstract Image

磷酸丝氨酸转氨酶1 (PSAT1)对肝缺血再灌注损伤的保护作用
肝缺血再灌注(I/R)损伤是一种严重的临床综合征,在世界范围内造成了深刻的医疗和社会经济负担。本研究旨在探索肝I/R损伤进展中的潜在生物标志物和治疗靶点。我们从gene expression Omnibus (GEO)数据库中筛选肝脏I/R损伤的基因表达谱,下载表达谱数据(GSE117066)。通过PPI网络聚类鉴定差异表达基因(DEGs),并基于基因本体(GO)、京都基因与基因组百科全书(KEGG)数据库进行富集途径。生物信息学分析用于鉴定减轻肝I/R损伤的生物标志物。最后,通过体外和体内实验研究了hub基因的作用。在假手术和I/R之间共提取162个基因(76个上调基因和86个下调基因),在I/R和缺血后适应(IPO)之间共提取248个基因(118个上调基因和130个下调基因)。采用PPI网络聚类和常见deg的最大团中心性(MCC)方法鉴定了磷酸丝氨酸转氨酶1 (PSAT1)作为肝I/R损伤的潜在基因。h - e、TUNEL和PCNA染色显示,I/R 6 h时肝损伤评分最高,凋亡相关蛋白表达水平与病理结果一致。功能增益和功能丧失试验均表明PSAT1可减轻肝I/R损伤。PSAT1可能在肝I/R损伤中发挥关键作用,因此可作为肝I/R损伤预后和个体化治疗的枢纽生物标志物。
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来源期刊
CiteScore
6.40
自引率
4.90%
发文量
40
期刊介绍: The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.
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