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pmid:38329418
Identification of renal ischemia reperfusion injury-characteristic genes, pathways and immunological micro-environment features through bioinformatics approaches.
Xinghua Lv · Qian Fan · Xuanjie Li · Peng Li · Zhanhai Wan · Xuena Han · Hao Wang · Xiaoxia Wang · Lin Wu · Bin Huo · Li Yang · Gen Chen · Yan Zhang
Aging · 2024 doi:10.18632/aging.205471
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Experiment
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Data
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Analysis
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Complete file
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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.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSIONS: 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.", "claims": [{"id": "claim-method", "statement": "Limma package [14] was performed to identify DEGs for the IRI stage vs. the control group for GSE98622 after transforming the FPKM to TPM.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38329418", "locator": "sections[4] \"Screening of DEGs\" paragraph 2", "quote": "Limma package [14] was performed to identify DEGs for the IRI stage vs. the control group for GSE98622 after transforming the FPKM to TPM."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The IRI RNA-Seq data and the corresponding clinical data were collected from the GEO database with accession numbers GSE98622, GSE182793, and GSE139107 (Table 1). 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