PDF(Pubmed)
Abstract：
Biomarkers and pathways associated with renal ischemia reperfusion injury (IRI) had not been well unveiled. This study was intended to investigate and summarize the regulatory networks for related hub genes. Besides, the immunological micro-environment features were evaluated and the correlations between immune cells and hub genes were also explored.
GSE98622 containing mouse samples with multiple IRI stages and controls was collected from the GEO database. Differentially expressed genes (DEGs) were recognized by the R package limma, and the GO and KEGG analyses were conducted by DAVID. Gene set variation analysis (GSVA) and weighted gene coexpression network analysis (WGCNA) had been implemented to uncover changed pathways and gene modules related to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle pathways, some novel pathways were also discovered to be critical in IRI. A series of novel genes associated with IRI was also dug out. An IRI mouse model was constructed to validate the results.
The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed. Furthermore, the immune infiltration for these samples was predicted and the results showed that macrophages infiltrated to the injured kidney to affect the tissue repair or fibrosis. Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration.
Consequently, the pathways, hub genes, miRNAs, and the immune microenvironment may explain the mechanism of IRI and might be the potential targets for IRI treatments.
GSE98622 containing mouse samples with multiple IRI stages and controls was collected from the GEO database. Differentially expressed genes (DEGs) were recognized by the R package limma, and the GO and KEGG analyses were conducted by DAVID. Gene set variation analysis (GSVA) and weighted gene coexpression network analysis (WGCNA) had been implemented to uncover changed pathways and gene modules related to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle pathways, some novel pathways were also discovered to be critical in IRI. A series of novel genes associated with IRI was also dug out. An IRI mouse model was constructed to validate the results.
The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed. Furthermore, the immune infiltration for these samples was predicted and the results showed that macrophages infiltrated to the injured kidney to affect the tissue repair or fibrosis. Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration.
Consequently, the pathways, hub genes, miRNAs, and the immune microenvironment may explain the mechanism of IRI and might be the potential targets for IRI treatments.
摘要：
背景：与肾缺血再灌注损伤（IRI）相关的生物标志物和途径尚未被很好地揭示。本研究旨在研究和总结相关hub基因的调控网络。此外,评估了免疫微环境特征，并探讨了免疫细胞与hub基因之间的相关性。
方法:从GEO数据库收集含有具有多个IRI阶段和对照的小鼠样品的GSE98622。差异表达基因(DEGs)被R包limma识别，GO和KEGG分析由DAVID进行。已实施基因集变异分析（GSVA）和加权基因共表达网络分析（WGCNA）以发现与IRI相关的改变的途径和基因模块。除了已知的途径，如凋亡途径，代谢途径，和细胞周期通路，还发现了一些新的途径在IRI中至关重要。还挖出了一系列与IRI有关的新基因。构建IRI小鼠模型以验证结果。
结果：众所周知的IRI标记基因（Kim1和Lcn2）和新的hub基因（Hbegf，Serpine2,Apbb1ip,Trip13，Atf3和Ncaph）已通过定量实时聚合酶链反应（qRT-PCR）得到证明。此后,预测靶向失调基因的miRNA并构建miRNA-靶网络。此外，预测了这些样本的免疫浸润，结果表明巨噬细胞浸润到受损的肾脏，影响组织修复或纤维化。Hub基因与巨噬细胞丰度显着正相关或负相关，表明它们在巨噬细胞浸润中起着至关重要的作用。
结论：因此，路径，集线器基因，miRNA,免疫微环境可以解释IRI的机制，并可能成为IRI治疗的潜在靶点。
方法:从GEO数据库收集含有具有多个IRI阶段和对照的小鼠样品的GSE98622。差异表达基因(DEGs)被R包limma识别，GO和KEGG分析由DAVID进行。已实施基因集变异分析（GSVA）和加权基因共表达网络分析（WGCNA）以发现与IRI相关的改变的途径和基因模块。除了已知的途径，如凋亡途径，代谢途径，和细胞周期通路，还发现了一些新的途径在IRI中至关重要。还挖出了一系列与IRI有关的新基因。构建IRI小鼠模型以验证结果。
结果：众所周知的IRI标记基因（Kim1和Lcn2）和新的hub基因（Hbegf，Serpine2,Apbb1ip,Trip13，Atf3和Ncaph）已通过定量实时聚合酶链反应（qRT-PCR）得到证明。此后,预测靶向失调基因的miRNA并构建miRNA-靶网络。此外，预测了这些样本的免疫浸润，结果表明巨噬细胞浸润到受损的肾脏，影响组织修复或纤维化。Hub基因与巨噬细胞丰度显着正相关或负相关，表明它们在巨噬细胞浸润中起着至关重要的作用。
结论：因此，路径，集线器基因，miRNA,免疫微环境可以解释IRI的机制，并可能成为IRI治疗的潜在靶点。
