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慢性肾脏病中铁死亡相关基因的鉴定

Identification of ferroptosis‑associated genes in chronic kidney disease.

作者信息

Shao Lishi, Fang Qixiang, Ba Chaofei, Zhang Yanqing, Shi Chen, Zhang Ya, Wang Jiaping

机构信息

Department of Radiology, Kunming Medical University and The Second Affiliated Hospital, Kunming, Yunnan 650500, P.R. China.

Department of Urology, The First Affiliated Hospital of The Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China.

出版信息

Exp Ther Med. 2022 Dec 8;25(1):60. doi: 10.3892/etm.2022.11759. eCollection 2023 Jan.

Abstract

Ferroptosis serves a pivotal role in developing chronic kidney disease (CKD). The present study aimed to detect and confirm the relevance of potential ferroptosis-related genes in CKD using bioinformatics and experimentation strategies. The original GSE15072 mRNA expression dataset was retrieved from the Gene Expression Omnibus database. Subsequently, the potential differentially expressed genes associated with ferroptosis of CKD were screened using R software. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses, correlation analysis and protein-protein interactions (PPI) were performed for differentially expressed ferroptosis-associated genes (DFGs). Lastly, the expression levels of the top nine DFGs were measured in the kidney tissue of Adriamycin-induced CKD rats and healthy controls via reverse transcription-quantitative (RT-q)PCR analysis. Overall, 49 DFGs among 21 patients with CKD and nine healthy controls were identified. GO and KEGG enrichment analyses demonstrated that these DFGs were primarily involved in 'ferroptosis' and 'mitophagy'. PPI findings indicated that these ferroptosis-associated genes interacted with one another. RT-qPCR of CKD tissue from the rat model revealed that STAT3, MAPK14, heat shock protein (HSP)A5, MTOR and solute carrier family 2 member 1 (SLC2A1) mRNA levels in CKD were upregulated. Overall, 49 potential ferroptosis-associated genes of CKD were identified via bioinformatics analyses. STAT3, MAPK14, HSPA5, MTOR and SLC2A1 may influence CKD onset by regulating ferroptosis. The present results add to the existing body of knowledge about CKD and may be useful in the treatment of CKD.

摘要

铁死亡在慢性肾脏病(CKD)的发展过程中起关键作用。本研究旨在运用生物信息学和实验策略,检测并确认CKD中潜在的铁死亡相关基因的相关性。原始的GSE15072 mRNA表达数据集从基因表达综合数据库中获取。随后,使用R软件筛选与CKD铁死亡相关的潜在差异表达基因。对差异表达的铁死亡相关基因(DFGs)进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析、相关性分析以及蛋白质-蛋白质相互作用(PPI)分析。最后,通过逆转录定量(RT-q)PCR分析,检测阿霉素诱导的CKD大鼠和健康对照的肾组织中排名前九的DFGs的表达水平。总体而言,在21例CKD患者和9例健康对照中鉴定出49个DFGs。GO和KEGG富集分析表明,这些DFGs主要参与“铁死亡”和“线粒体自噬”。PPI结果表明,这些铁死亡相关基因相互作用。大鼠模型CKD组织的RT-qPCR显示,CKD中信号转导和转录激活因子3(STAT3)、丝裂原活化蛋白激酶14(MAPK14)、热休克蛋白(HSP)A5、雷帕霉素靶蛋白(MTOR)和溶质载体家族2成员1(SLC2A1)的mRNA水平上调。总体而言,通过生物信息学分析鉴定出49个CKD潜在的铁死亡相关基因。STAT3、MAPK14、HSPA5、MTOR和SLC2A1可能通过调节铁死亡影响CKD的发病。目前的结果丰富了关于CKD的现有知识体系,可能对CKD的治疗有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/9780523/204e1a7bc159/etm-25-01-11759-g00.jpg

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