Bioinformatic Analyses of Renal Ischaemia-Reperfusion Injury Models: Identification of Key Genes Involved in the Development of Kidney Disease

Abstract

Background/Aims: To develop a novel strategy for the treatment of kidney disease, we explored potential molecular targets involved in the development of renal ischaemia-reperfusion injury (IRI). Methods: The Gene expression profile data of GSE27274, including controls and rats subjected to renal IRI and reperfusion for 24 h (IR24) or 120 h (IR120), was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analysed using the limma package. Gene Ontology (GO) and pathway functional enrichment analyses of common DEGs were carried out. Protein-protein interactions (PPI) and miRNA-DEG network analyses were performed using the STRING database and WebGestalt, respectively, followed by network construction using Cytoscape. Results: In total, 80 common DEGs (41 up- and 39 downregulated genes) between IR24 and IR120 were screened. Genes encoding tissue inhibitor of matrix metalloproteinase-1 (Timp1), secreted phosphoprotein 1 (Spp1) and dimethylglycine dehydrogenase (Dmgdh) were identified as hub genes in the PPI network and may be significant in the development of renal IRI. Upregulated Spp1 was enriched in the inflammatory response, and downregulated Dmgdh was enriched in the catabolic process of the amino acid betaine. In reactome pathway analyses, Spp1 was enriched in toll-like receptor signalling, and Dmgdh was enriched in glycine, serine and threonine metabolic pathways. The common DEGs were mainly regulated by 15 miRNA clusters. Conclusion: Timp1, Spp1, Dmgdh, miR-142-5p and miR-181a may be potential targets or biomarkers for the development of renal IRI.

Sevoflurane Postconditioning Attenuates Hepatic Ischemia-Reperfusion Injury by Limiting HMGB1/TLR4/NF-κB Pathway via Modulating microRNA-142 in vivo and in vitro

“…As shown in Figure 3C, the miR-142 expression levels were significantly reduced in HIRI group, compared with Sham group, however, this inhibitory effect was dramatically reversed by Sevo postconditioning. Previous studies have reported that miR-142 plays important roles in regulating I/R injury in other organs, such as kidney and heart (Zhu et al, 2018;; thus, we proposed that Sevo postconditioning may improve hepatic I/R injury by reverting I/R-induced downregulation of miR-142.…”

“…In this study, microarray screening revealed miR-142 was one of the major miRNAs that were upregulated in mice by Sevo treatment. Previous studies have demonstrated that miR-142 improved I/R injury in different organs including heart (Su et al, 2019) and kidney (Zhu et al, 2018); however, whether miR-142 is involved in the protective mechanisms of Sevo postconditioning in hepatic I/R injury remains unknown. In our findings, it was confirmed that the agomir-142 injection enhanced the protective effects when compared with Sevo, while the antagomir-142 injection suppressed the therapeutic effects of Sevo in mice.…”

Deiminated proteins and extracellular vesicles - Novel serum biomarkers in whales and orca

“…It is a mitochondrial matrix enzyme with roles in choline degradation, one-carbon metabolism and electron transfer to the respiratory chain (Augustin et al, 2016). DMGDH is a key metabolic enzyme, linked to diabetes, kidney disease (Zhu et al, 2018;Magnusson et al, 2015), carcinoma and metastasis (Liu et al, 2016).…”

Investigation of the underlying hub genes and mechanisms of reperfusion injury in patients undergoing coronary artery bypass graft surgery by integrated bioinformatic analyses

“…Although various bioinformatics analyses of reperfusion in other organs and animals have been performed, a systematic and thorough analysis of cardiac IR in human hearts is still lacking (17,18). Therefore, in this study, a co-expression correlation network was constructed using the expression data from the gene expression omnibus (GEO) database.…”