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Proteomics to Metabolomics: A New Insight into the Pathogenesis of Hypertensive Nephropathy

蛋白质组 蛋白质组学 发病机制 生物 细胞生物学 化学 生物化学 内分泌学 基因 免疫学
作者
Yasin Eshraghi,Maryam Abedi,Yousof Gheisari
出处
期刊:Kidney & Blood Pressure Research [S. Karger AG]
卷期号:48 (1): 710-726 被引量:1
标识
DOI:10.1159/000534354
摘要

<b><i>Background:</i></b> Hypertensive nephropathy (HN) is a high-burden disorder and a leading cause of end-stage renal disease. Despite huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to providing a comprehensive insight into this complex disorder. <b><i>Methods:</i></b> Proteome profiles of kidney tubulointerstitium and outer and inner cortex from a rat model of HN were retrieved from the proteomics identification database, and the quality of the datasets was assessed. Proteins that exhibited differential expression were detected and their interactions were analyzed in the kidney sub-compartments. Furthermore, enzymes were linked to the attributed metabolites. Functional enrichment analyses were performed to identify key pathways and processes based on the differentially expressed proteins and predicted metabolites. <b><i>Results:</i></b> Proteasome-mediated protein degradation, actin cytoskeleton organization, and Rho GTPase signaling pathway are involved in the pathogenesis of HN. Furthermore, tissue hypoxia and dysregulated energy homeostasis are among the key underlying events. The metabolism of purine and amino acids is also affected in HN. <b><i>Conclusion:</i></b> Although the proposed pathogenic mechanisms remain to be further validated in experimental studies, this study contributes to the understanding of the molecular mechanisms of HN through a systematic unsupervised approach. Considering the significant alterations of metabolic pathways, HN can be viewed as an “acquired error of metabolism.”
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