iTRAQ-Based Comparative Proteomics Analysis of Urolithiasis Rats Induced by Ethylene Glycol

Abstract

Nephrolithiasis is a frequent chronic urological condition with a high prevalence and recurrence rate. Proteomics studies on urolithiasis rat models are highly important in characterizing the pathophysiology of kidney stones and identifying potential approaches for preventing and treating kidney stones. The isobaric tags for relative and absolute quantification (iTRAQ) were performed to identify differentially expressed proteins (DEPs) in the kidney between urolithiasis rats and control rats. The results showed that 127 DEPs (85 upregulated and 42 downregulated) were identified in urolithiasis and control rats. The functions of DEPs were predicted by Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein–protein interaction (PPI) network analysis. The expression of four upregulated proteins (Tagln, Akr1c9, Spp1, and Fbn1) and four downregulated proteins (Hbb, Epb42, Hmgcs2, and Ca1) were validated by parallel reaction monitoring (PRM). Proteomics studies of ethylene glycol-induced urolithiasis rat models using iTRAQ and PRM helped to elucidate the molecular mechanism governing nephrolithiasis and to identify candidate proteins for the treatment of kidney stones.

Spaceflight causes strain dependent gene expression changes associated with lipid and extracellular matrix dysregulation in the mouse kidney in vivo

“…The Hmgcs2 gene encodes the protein 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA synthase) which catalyses the conversion of acetyl-CoA and acetoacetyl-CoA to HMG-CoA and CoA, a which is a rate-limiting step in ketogenesis [36](Hegardt, 1999). Impairment of ketogenesis causes hepatic injury and inflammation [37](Cotter et al ., 2014) and downregulation of HMG-CoA synthase has been identified as a marker for kidney stone disease in a model of induced urolithiasis in rats [38](Cao et al ., 2020); suggesting that the downregulation of HMG-CoA synthase in our data may be a marker for kidney injury.…”

Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis

“…To verify the key value of 6 IRGs in vivo, renal stone model was established by adding 1% ethylene glycol (EG) (324558, Sigma-Aldrich, USA) in drinking water for 4 weeks, as described in our previous study (17). The animal experiment was approved by the Ethics Committee for Animal Research of the Xiangya hospital of Central South University (202301003).…”