Proteomics to metabolomics: A new insight into the pathogenesis of hypertensive nephropathy

Abstract

Abstract Background: Hypertensive nephropathy (HN) is a high burden disorder and a leading cause of end-stage renal disorder. In spite of huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to provide a comprehensive insight towards this complex disorder. Methods: Protein expression profiles of kidney tubule and cortex sub-compartments were retrieved from the PRIDE database and the quality of the datasets were assessed using principal component analysis (PCA) and hierarchical clustering. Differentially expressed proteins (DEPs) were detected and their attributed metabolites were enriched and their interactions were assessed in multi-layer networks. Moreover, considering the DEPs and the predicted metabolites, key biomedical phenomena with a leading role in HN pathogenesis were proposed. Results: Amino acid and purine metabolisms are the most prominent alteration in kidney cortex whereas dysregulation of energy hemostasis is a key pathogenic mechanism in tubule. Besides, actin cytoskeleton disorganization is an enriched pathway in both anatomical areas. Conclusion: The proteomics profiles of kidney sub-compartments were analyzed using a top-down approach to infer the main pathogenic processes. The constructed holistic map of HN can be exploited to propose novel therapeutic strategies. Keywords: Hypertensive nephropathy, Proteomics, Metabolomics, Systems biology