Quantitative Proteome of Infant Stenotic Ureters Reveals Extracellular Matrix Organization and Oxidative Stress Dysregulation Underlying Ureteropelvic Junction Obstruction.

PURPOSE Ureteropelvic junction obstruction (UPJO) is the most frequent cause of congenital hydronephrosis in child. To better investigate the molecular mechanisms of this pathological process, we compared the stenotic ureter proteome of UPJO in infants with their own normal pre-stenotic segments. EXPERIMENTAL DESIGN: We performed data independent acquisition-based proteomics to compare proteome between pre-stenotic and stenotic ureter from nine UPJO infants (six of nine high-quality control samples were finally included). Gene Ontology analysis, hierarchical cluster analysis and network interaction were performed to characterize biological functions of significantly altered proteins. Selected significantly altered proteins were validated by western blot on another three UPJO infants. RESULTS 15 proteins were up-regulated and 33 proteins were down-regulated during stenotic pathology. Significantly altered proteins were involved in decreased extracellular matrix and cytoskeleton organization, increased regulation of oxidative activity and altered inflammatory associated exocytosis. Significant expression of Biglycan, Fibulin-1, Myosin-10, Cytochrome b5 were validated by western blot, providing possible mechanism in UPJO which could be associated impaired smooth muscle cell, epithelial integrity and increased oxidative stress. CONCLUSIONS AND CLINICAL RELEVANCE: This proteomic study provides molecular evidence of dysregulated extracellular matrix organization, impaired smooth muscle cell and oxidative stress during UPJO pathology, indicating that Biglycan, Fibulin-1, Myosin-10, Cytochrome b5 might reflect the pathology of UPJO and further studies are still needed to investigate their clinical potential. This article is protected by copyright. All rights reserved.