Investigation into the underlying molecular mechanisms of hypertensive nephrosclerosis using bioinformatics analyses

Abstract

Hypertensive nephrosclerosis (HNS) is a major risk factor for end-stage renal disease. However, the underlying pathogenesis of HNS remains to be fully determined. The gene expression profile of GSE20602, which consists of 14 glomeruli samples from patients with HNS and 4 normal glomeruli control samples, was obtained from the Gene Expression Omnibus database. Gene ontology (GO) and pathway enrichment analyses were performed in order to investigate the functions and pathways of differentially expressed genes (DEGs). Pathway relation and co-expression networks were constructed in order to identify key genes and signaling pathways involved in HNS. In total, 483 DEGs were identified to be associated with HNS, including 302 upregulated genes and 181 downregulated genes. Furthermore, GO analysis revealed that DEGs were significantly enriched in the small molecule metabolic process. In addition, pathway analysis also revealed that DEGs were predominantly involved in metabolic pathways. The tricarboxylic acid (TCA) cycle was identified as the hub pathway in the pathway relation network, whereas the sorbitol dehydrogenase (SORD) and cubulin (CUBN) genes were revealed to be the hub genes in the co-expression network. The present study revealed that the SORD, CUBN and albumin genes as well as the TCA cycle and metabolic pathways are involved in the pathogenesis of HNS. The results of the present study may contribute to the determination of the molecular mechanisms underlying HNS, and provide insight into the exploration of novel targets for the diagnosis and treatment of HNS.

Gene Expression Studies and Targeted Metabolomics Reveal Disturbed Serine, Methionine, and Tyrosine Metabolism in Early Hypertensive Nephrosclerosis

“…Although there is no very good animal model for nephrosclerosis, current experimental data indicate decreased citric acid (TCA)-cycle activity 20 and extensive mitochondrial abnormalities and dysfunctions in kidneys exposed to various forms of hypertension 21 . Pathway analysis based on gene expression in human nephrosclerosis biopsies indicate that amino acid metabolism (including arginine, serine, and tryptophan metabolisms), TCA-cycle, glycolysis/gluconeogenesis, fatty acid oxidation, peroxisome proliferator–activated receptor signaling, and others were significantly disturbed 22 …”

Introducing Serine as Cardiovascular Disease Biomarker Candidate via Pathway Analysis

“…In this document alteration in urine execration of 11 amino acid including serine is reported [22]. Distribution of amino acid metabolism counting serine, fatty acid oxidation, and tricarboxylic acid cycle in human nephrosclerosis biopsies via pathway analysis is reported by Liu et al (2018) [23]. Direct blood pressure-lowering effects of serine is reported by Mishra et al [24]; hence, it can be expected that decrement of serine leads to a significant alteration in blood pressure control.…”

“…Distribution of amino acid metabolism counting serine, fatty acid oxidation, and tricarboxylic acid cycle in human nephrosclerosis biopsies via pathway analysis is reported by Liu et al . (2018) [ 23 ]. Direct blood pressure–lowering effects of serine is reported by Mishra et al .…”

Comprehensive Bioinformatics Analysis Identifies POLR2I as a Key Gene in the Pathogenesis of Hypertensive Nephropathy

“…The focus of our study was to investigate the molecular mechanisms of tubulointerstitial lesions in the HN rather than glomerular lesions (Cui et al, 2017;Liu et al, 2018). It is based on the hypothesis that subtle tubulointerstitial lesions are not merely the manifestation of HN but an underlying cause of hypertension (Johnson et al, 2002).…”