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.

Highlights

  • To reduce the prevalence and recurrence rate of kidney stones, it is urgently needed to have a better understanding of the underlying mechanisms involved in nephrolithiasis based on highthroughput biotechnology

  • The structure of the renal parenchyma was destroyed by calcium oxalate (CaOx) crystals from the nephrolithiasis group

  • The results showed that differentially expressed proteins (DEPs) in nephrolithiasis rats compared with the control rats were involved in 117 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways

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Summary

Introduction

Kidney stones are mineral deposits from renal papillae, and 80% of stones are calcium stones composed of calcium oxalate (CaOx) mixed with calcium phosphate [1]. Nephrolithiasis is a frequent chronic urological disease. The incidence and prevalence of kidney stones consistently increased in the past 3–4 decades globally, while the costs associated with stone disease have increased [2]. 67% of first-time symptomatic stone formers had stone recurrence at 5 years [3]. Patients with stones are at risk of hypertension, chronic kidney disease, and end-stage renal disease, resulting in heavy economic and social burden [6, 7]. To reduce the prevalence and recurrence rate of kidney stones, it is urgently needed to have a better understanding of the underlying mechanisms involved in nephrolithiasis based on highthroughput biotechnology

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