Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4440-4448. doi: 10.3892/mmr.2018.8405. Epub 2018 Jan 9.
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.
高血压性肾硬化症(HNS)是终末期肾病的主要危险因素。然而,HNS 的潜在发病机制仍有待充分确定。从基因表达综合数据库中获取了 GSE20602 的基因表达谱,该数据集由 14 个来自 HNS 患者的肾小球样本和 4 个正常肾小球对照样本组成。进行基因本体论(GO)和通路富集分析,以研究差异表达基因(DEGs)的功能和通路。构建通路关系和共表达网络,以鉴定与 HNS 相关的关键基因和信号通路。总共鉴定出 483 个与 HNS 相关的 DEGs,包括 302 个上调基因和 181 个下调基因。此外,GO 分析表明,DEGs 显著富集于小分子代谢过程。此外,通路分析还表明,DEGs 主要参与代谢途径。三羧酸(TCA)循环被确定为通路关系网络中的枢纽通路,而山梨醇脱氢酶(SORD)和 cubulin(CUBN)基因被确定为共表达网络中的枢纽基因。本研究表明,SORD、CUBN 和白蛋白基因以及 TCA 循环和代谢途径参与了 HNS 的发病机制。本研究的结果可能有助于确定 HNS 的分子机制,并为探索 HNS 的诊断和治疗新靶点提供思路。