The Correlation Between Endoplasmic Reticulum Stress And Kidney Stones

ObjectiveKidney stone formation is a complex biological process involving renal tubular epithelial cells,organic proteins,and inorganic salts.This study intends to find the critical biological processes of kidney stone formation by urinary proteomic data and to analyze the effect of urinary inorganic pyrophosphate on infectious kidney stones.MethodsData of proteins associated with kidney stone were derived from a urinary proteomics study of kidney stone and Polysearch software search.Differentially expressed proteins were integrated into the "In Web" PPI(protein-protein interaction)database to construct a kidney stone PPI network,and the network was visualized using a Cytoscape software.Proteins enrichment was analyzed using Gene Ontology(GO)to identify key "biological processes" of kidney stones.The finding was further validated in vivo by molecular cell biology methods.Also,we observed the inhibitory effect of pyrophosphate on urinary tract infection using K-B paper method.ResultsEight hundred thirty-seven kidney stone-associated proteins were collected and was integrated into the"In Web"protein-protein interaction database to construct a network of kidney stone,including 340 proteins and 740 edges.GO analysis revealed that proteins are enriched in endoplasmic reticulum-related biological processes such as"protein stabilization","protein folding"and "ATF6 regulates unfolded protein response","endoplasmic reticulum complex",etc.These findings suggest that endoplasmic reticulum dysfunction may be a critical biological process in the formation of kidney stone.Further rat animal models of kidney stones were used to detect endoplasmic reticulum-related marker proteins.The expression of Bip/GRP78 and CHOP was increased,suggesting endoplasmic reticulum stress occurs during kidney stone formation;the findings of increased expression of PERK and ATF6 and mRNA splicing of XBP1 suggest that endoplasmic reticulum stress occurs through three major pathways;the finding of increased expression of Caspase-12 and Caspase-3 protein suggests that endoplasmic reticulum stress is involved in apoptosis during stone formation.The results demonstrate that endoplasmic reticulum stress is a critical biological process in the formation of kidney stones.Also,the effect of urinary inorganic pyrophosphate salt on kidney stones was observed in the study.The growth of Escherichia coli and Staphylococcus aureus were inhibited,suggesting pyrophosphate has a significant antibacterial effect.ConclusionsThe endoplasmic reticulum stress is a critical biological process of kidney stones formation.A pyrophosphate has a significant antibacterial effect on infec tious kidney stones.