Identification of hub genes associated with acute kidney injury induced by renal ischemia-reperfusion injury in mice

Sheng He; Lili He; Fangran Yan; Junda Li; Xiaoting Liao; Maoyao Ling; Ren Jing; Linghui Pan

doi:10.3389/fphys.2022.951855

Identification of hub genes associated with acute kidney injury induced by renal ischemia-reperfusion injury in mice

Front Physiol. 2022 Sep 29:13:951855. doi: 10.3389/fphys.2022.951855. eCollection 2022.

Authors

Sheng He^{1

2

3

4

5}, Lili He⁶, Fangran Yan¹, Junda Li¹, Xiaoting Liao¹, Maoyao Ling¹, Ren Jing¹, Linghui Pan^{1

2

3

4}

Affiliations

¹ Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, China.
² Guangxi Engineering Research Center for Tissue and Organ Injury and Repair Medicine, Nanning, China.
³ Guangxi Key Laboratory for Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, China.
⁴ Guangxi Clinical Research Center for Anesthesiology, Nanning, China.
⁵ Department of Anesthesiology, The First Affiliated Hospital of Southern China University, Hengyang, China.
⁶ Department of Anesthesiology, The Second Affiliated Hospital of Southern China University, Hengyang, China.

Abstract

Background: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia-reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia-reperfusion injury (IRI-AKI). Method: Two public datasets (GSE39548 and GSE131288) originating from the NCBI Gene Expression Omnibus (GEO) database were analyzed using the R software limma package, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) and gene set enrichment analysis (GSEA) were performed using the differentially expressed genes. Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes, and transcription factor (TF)-hub gene and miRNA-hub gene networks were constructed. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb. Result: A total of 323 common differentially expressed genes were identified in the renal ischemia-reperfusion injury group compared with the control group. Among these, 260 differentially expressed genes were upregulated and 66 differentially expressed genes were downregulated. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis results showed that these common differentially expressed genes were enriched in positive regulation of cytokine production, muscle tissue development, and other biological processes, indicating that they were involved in mitogen-activated protein kinase (MAPK), PI3K-Akt, TNF, apoptosis, and Epstein-Barr virus infection signaling pathways. Protein-protein interaction analysis showed 10 hub genes, namely, Jun, Stat3, MYC, Cdkn1a, Hif1a, FOS, Atf3, Mdm2, Egr1, and Ddit3. Using the STRUST database, starBase database, and DGIdb database, it was predicted that 34 transcription factors, 161 mi-RNAs, and 299 drugs or molecular compounds might interact with hub genes. Conclusion: Our findings may provide novel potential biomarkers and insights into the pathogenesis of ischemia-reperfusion injury-acute kidney injury through a comprehensive analysis of Gene Expression Omnibus data, which may provide a reliable basis for early diagnosis and treatment of ischemia-reperfusion injury-acute kidney injury.

Keywords: MYC; Stat3; acute kidney injury; hub genes; ischemia reperfusion.