Deng Yinzhi, Luo Hesheng
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
J Cell Commun Signal. 2023 Sep;17(3):851-862. doi: 10.1007/s12079-023-00727-0. Epub 2023 Feb 6.
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.
肝缺血再灌注（I/R）损伤是一种严重的临床综合征，在全球范围内造成了沉重的医学和社会经济负担。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。我们从基因表达综合数据库（GEO）中筛选了肝I/R损伤的基因表达谱，下载了表达谱数据（GSE117066）。通过蛋白质-蛋白质相互作用（PPI）网络聚类鉴定差异表达基因（DEGs），并基于基因本体论（GO）、京都基因与基因组百科全书（KEGG）数据库进行富集通路分析。采用生物信息学分析来鉴定减轻肝I/R损伤的生物标志物。最后，通过体外和体内实验研究了枢纽基因的作用。在假手术组和I/R组之间共提取了162个DEGs（76个上调基因和86个下调基因），在I/R组和缺血后处理（IPO）组之间提取了248个DEGs（118个上调基因和130个下调基因）。通过PPI网络聚类和共同DEGs的最大团中心性（MCC）方法，确定磷酸丝氨酸转氨酶1（PSAT1）为肝I/R损伤的潜在基因。然后，苏木精-伊红（H-E）染色、末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色和增殖细胞核抗原（PCNA）染色表明，肝损伤评分在I/R 6小时时最高。凋亡相关蛋白的表达水平与病理结果一致。功能获得和功能缺失试验均表明，PSAT1可减轻肝I/R损伤。PSAT1可能在肝I/R损伤中起关键作用，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。
