Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, PR China.
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province 510030, PR China.
Int Immunopharmacol. 2020 Apr;81:106246. doi: 10.1016/j.intimp.2020.106246. Epub 2020 Feb 7.
Ischemia reperfusion injury (IRI) is a major challenge for renal transplantation. This study was performed to explore the mechanisms and potential molecular targets involved in renal IRI. In this study, the gene datasets GSE43974 and GSE126805 from the Gene Expression Omnibus database, which include ischemic and reperfused renal specimens, were analyzed to determine differentially expressed genes (DEGs). Gene ontology annotations, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis were performed to determine the pathways that are significantly enriched during ischemia and reperfusion. We also determined the microenvironment cell types xCell and performed correlation analyses to reveal the relationship between the molecular pathways and microenvironment cell infiltration. We found 77 DEGs (76 up- and 1 downregulated) and 323 DEGs (312 up- and 11 downregulated) in the GSE43974 and GSE126805 datasets, respectively. Similar signaling pathway enrichment patterns were observed between the two datasets. The combined analyses demonstrate that the NOD-like receptor signaling pathway and its two downstream signaling pathways, MAPK and NF-kβ, are the major significantly enriched pathways. The xCell analysis identified immune cells that are significantly changed after reperfusion, including hematopoietic stem cells, M2 macrophages, monocytes, Treg cells, conventional dendritic cells, and pro B-cells. Enrichment scores of the NOD-like receptor signaling pathway and its downstream pathways during IRI was significantly correlated with the change levels in class-switched memory B-cell and hematopoietic stem cells in both datasets. These data reveal the important role of the NOD-like receptor signaling pathway during IRI, and the close relationship between this pathway and infiltration of specific immune cell types. Our data provide compelling insights into the pathogenesis and potential therapeutic targets for renal IRI.
缺血再灌注损伤（IRI）是肾移植的主要挑战。本研究旨在探讨肾 IRI 涉及的机制和潜在的分子靶点。本研究分析了基因表达综合数据库中的基因数据集 GSE43974 和 GSE126805，这些数据集包含缺血和再灌注的肾标本，以确定差异表达基因（DEGs）。进行基因本体注释、京都基因与基因组百科全书分析和基因集富集分析，以确定在缺血和再灌注过程中显著富集的途径。我们还确定了微环境细胞类型 xCell，并进行了相关性分析，以揭示分子途径与微环境细胞浸润之间的关系。我们在 GSE43974 和 GSE126805 数据集中分别发现了 77 个 DEGs（76 个上调和 1 个下调）和 323 个 DEGs（312 个上调和 11 个下调）。两个数据集之间观察到相似的信号通路富集模式。联合分析表明，NOD 样受体信号通路及其两个下游信号通路 MAPK 和 NF-kβ 是主要显著富集的途径。xCell 分析确定了再灌注后显著变化的免疫细胞，包括造血干细胞、M2 巨噬细胞、单核细胞、Treg 细胞、常规树突状细胞和前 B 细胞。IRI 过程中 NOD 样受体信号通路及其下游通路的富集评分与两个数据集中转录因子 EB 激活的记忆 B 细胞和造血干细胞的变化水平显著相关。这些数据揭示了 NOD 样受体信号通路在 IRI 中的重要作用，以及该通路与特定免疫细胞类型浸润之间的密切关系。我们的数据为肾 IRI 的发病机制和潜在治疗靶点提供了有说服力的见解。
