Bioinformatic analysis reveals novel hub genes and pathways associated with hypertensive nephropathy

Abstract

Aim Hypertensive nephropathy (HTN) is one of the leading causes of end‐stage renal disease and is closely associated with inflammation and tubule‐interstitial fibrosis. The molecular mechanism underlying HTN remains unclear. This study used bioinformatic analysis to identify the novel gene targets for HTN. Methods We downloaded the microarray data of GSE99325 and GSE32591 from Gene Expression Omnibus. The dataset comprised 20 HTN and 15 normal samples. The differentially expressed genes (DEG) were identified, and then gene ontology (GO) enrichment was performed, and a GO tree was constructed by using clusterProfiler and ClueGO. In addition, a protein–protein interaction network was established using the Search Tool for the Retrieval of Interacting Genes database and visualized by Cytoscape. The novel hub genes were validated in in vitro experiments. Results A total of 267 genes (117 up‐regulated and 150 down‐regulated genes) were identified as DEG. GO analysis and the GO tree indicated that the DEG were mainly associated with steroid hormone response and the extracellular matrix. Based on the protein–protein interaction network, we screened out several novel hub genes. Considering the findings and the literature review, we focused on and validated the dual specificity phosphatase 1, tissue inhibitor of matrix metalloproteinases 1, fos proto‐oncogene and jun proto‐oncogenes, which may play significant roles in the pathogenesis of HTN. These findings were consistent with the bioinformatic results for the in vitro validation. Conclusion This study identified for the first time novel hub genes with microarray data in HTN by using bioinformatic analysis and provided novel evidence and clues for future works.

Current perspectives and trends of the research on hypertensive nephropathy: a bibliometric analysis from 2000 to 2023

“…With the development of sequencing techniques and bioinformatics, more mechanisms underlying HTN have been disclosed. The novel pivotal genes have been initially identified through microarray data using bioinformatic analysis [ 82 ]. Ferroptosis has been found to play a role in HTN through pathways such as branched-chain amino acid metabolism and retinol metabolism, and biological processes such as organic and amino acid metabolism and humoral immunity [ 29 ].…”

Minichromosome maintenance 6 protects against renal fibrogenesis by regulating DUSP6-mediated ERK/GSK-3β/Snail1 signaling

“…Reduced DUSP1, DUSP4, DUSP6, DUSP10, and DUSP26 expression has been reported in diabetic nephropathy [32][33][34]. DUSP1 and DUSP5 are downregulated in hypertensive nephropathy [35,36],…”

Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods

“…For example, in an early methodological innovation [ 64 ], researchers integrated the differential expression attribute of genes with information on pathway member sharing and showed that groups at the pathway interfaces were more relevant to leukemia subtype distinction. In another example of bioinformatics analysis of hypertensive nephropathy [ 65 ], the authors used a functionality through GOSemSim [ 66 ] to sketch a function term connection network, whereby they focused attention to genes associated with the bridging terms (terms forming the boundaries of network modules). In the present study, we laid out a differential-network-assisted pathway crosstalk analysis workflow ( Figure 1 ), demonstrating its validity in mining SCZ-relevant rewired pathways, disrupted pathway crosstalk circuits, and critical genes and gene links.…”