Exploring the role of Hmox1 in ferroptosis and immune infiltration during renal ischemia-reperfusion injury
作者全名："Luo, Jin; Pei, Jun; Yu, Cheng-jun; Tian, Xiao-mao; Zhang, Jie; Shen, Lian-ju; Hua, Yi; Wei, Guang-Hui"
作者地址："[Luo, Jin; Pei, Jun; Yu, Cheng-jun; Tian, Xiao-mao; Zhang, Jie; Shen, Lian-ju; Hua, Yi; Wei, Guang-Hui] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Urol, Minist Educ,Key Lab Child Dev & Disorders,Children, Chongqing, Peoples R China; [Luo, Jin; Pei, Jun; Yu, Cheng-jun; Tian, Xiao-mao; Zhang, Jie; Shen, Lian-ju; Hua, Yi; Wei, Guang-Hui] Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing, Peoples R China; [Hua, Yi; Wei, Guang-Hui] Chongqing Med Univ, Dept Urol, Childrens Hosp, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China"
通信作者："Hua, Y; Wei, GH (通讯作者)，Chongqing Med Univ, Dept Urol, Childrens Hosp, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China."
来源：RENAL FAILURE
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001067217800001
JCR分区：Q1
影响因子：3
年份：2023
卷号：45
期号：2
开始页：
结束页：
文献类型：Article
关键词：Kidney transplantation; biomarkers; protein-protein interaction network; endogenous RNAs; immunological infiltration
摘要："Ischemia-reperfusion injury (IRI) is inevitable in kidney transplantations and, as a complex pathophysiological process, it can be greatly impacted by ferroptosis and immune inflammation. Our study aimed to identify the biomarkers of renal IRI (RIRI) and elucidate their relationship with immune infiltration. In this study, the GSE148420 database was used as a training set to analyze differential genes and overlap them with ferroptosis-related genes to identify hub genes using a protein-protein interaction (PPI) network, the least absolute shrinkage and selection operator (LASSO), and random forest algorithm (RFA). We verified the hub gene and ferroptosis-related phenotypes in a verification set and animal experiments involving unilateral IRI with contralateral nephrectomy in rats. Gene set enrichment analysis (GSEA) of single genes was conducted according to the hub gene to predict related endogenous RNAs (ceRNAs) and drugs to establish a network. Finally, we used the Cibersort to analyze immunological infiltration and conducted Spearman's correlation analysis. We identified 5456 differential genes and obtained 26 ferroptosis-related differentially expressed genes. Through PPI, LASSO, and RFA, Hmox1 was identified as the only hub gene and its expression levels were verified using verification sets. In animal experiments, Hmox1 was verified as a key biomarker. GSEA of single genes revealed the seven most related pathways, and the ceRNAs network included 138 mRNAs and miRNAs. We predicted 11 related drugs and their three-dimensional structural maps. Thus, Hmox1 was identified as a key biomarker and regulator of ferroptosis in RIRI and its regulation of ferroptosis was closely related to immune infiltration."
基金机构："Jin Luo: Conceptualization, Methodology, Investigation, Formal analysis, Writing - Original Draft, Visualization; Jun Pei: Methodology, Software, Writing - Original Draft, Visualization; Cheng-jun Yu: Investigation, Formal analysis, Writing - Review amp;a"
基金资助正文："Jin Luo: Conceptualization, Methodology, Investigation, Formal analysis, Writing - Original Draft, Visualization; Jun Pei: Methodology, Software, Writing - Original Draft, Visualization; Cheng-jun Yu: Investigation, Formal analysis, Writing - Review & amp; Editing; Xiao-mao Tian: Methodology, Software, Writing - Review & amp; Editing; Jie Zhang: Conceptualization, Investigation, Formal analysis; Lian-ju Shen: Writing - Review & amp; Editing, Supervision; Yi Hua: Conceptualization, Methodology, Supervision, Writing - Review & amp; Editing; Guang-Hui Wei: Conceptualization, Project administration."
