The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods

Abstract

Transmission of biological information is a biochemical process of multistep cascade from genes/proteins to metabolites. However, because most metabolites reflect the terminal information of the biochemical process, it is difficult to describe the transmission process of disease information in terms of the metabolomics strategy. In this paper, by incorporating network and metabolomics methods, an integrated approach was proposed to systematically investigate and explain the molecular mechanism of renal interstitial fibrosis. Through analysis of the network, the cascade transmission process of disease information starting from genes/proteins to metabolites was putatively identified and uncovered. The results indicated that renal fibrosis was involved in metabolic pathways of glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, riboflavin metabolism, tyrosine metabolism, and sphingolipid metabolism. These pathways involve kidney disease genes such as TGF-β1 and P2RX7. Our results showed that combining metabolomics and network analysis can provide new strategies and ideas for the interpretation of pathogenesis of disease with full consideration of "gene-protein-metabolite."

Urinary metabolomics reveals the therapeutic effect of HuangQi Injections in cisplatin-induced nephrotoxic rats

“…The dysregulations of fatty acids including tetracosanoic acid, octadecanamide, docosatrienoic acid, 9-oxooctadecanoic acid, palmitic acid, arachidonic acid and eicosatrienoic acid were demonstrated in both patients with chronic kidney disease and animal models 50–53 . It was reported that single CDDP dose could lead to the accumulation of nonesterified fatty acids and triglycerides in serum, urine and kidney tissue, while the activation of intracellular calcium-independent phospholipase A2 (PA2) and the inhibition of mitochondrial fatty acid oxidation were considered as the potential mechanisms responsible for the accumulation of free fatty acids 5 .…”

Identification of key metabolic changes during liver fibrosis progression in rats using a urine and serum metabolomics approach

“…Metabolomics is the latest systems biology technique for identification of global metabolic profile changes of endogenous substances in biological systems and may be used to characterize the different physiological and pathological states of organisms under external physical, chemical and environmental stimuli 5 , 6 . Recently, metabolomics has been extensively used in the diagnosis and monitoring of disease progression, providing crucial insights into disease pathogenesis 7 .…”

Kidney Tissue Targeted Metabolic Profiling of Unilateral Ureteral Obstruction Rats by NMR

“…1 H NMR-based metabolomics have been used in many renal related studies, such as identification of the pathogenesis of diabetic nephropathy (Wei et al, 2015 ), evaluation of renal transplant dysfunction (Serkova et al, 2005 ), prediction of renal function after obstruction relief (Dong et al, 2013 ) and detection of drug induced nephrotoxicity (Sieber et al, 2009 ). Metabolomic analysis of RIF using UUO model has extracted significant biological information and assessed the endogenous metabolite changes in serum, urine, and kidney samples, which has deepened the understanding of the pathogenesis of RIF and offered invaluable information for diagnosis and therapy treatment of RIF (Maclellan et al, 2011 ; Zhang et al, 2012 ; Fang et al, 2016 ; Xiang et al, 2016 ; Zhao et al, 2016 ).…”