Quantitative Proteome of Infant Stenotic Ureters Reveals Extracellular Matrix Organization and Oxidative Stress Dysregulation Underlying Ureteropelvic Junction Obstruction
| Autor: | Junqi Zhang, Zhoutong Chen, Hongquan Geng, Yueyan Li, Qimin Zhang, Maosheng Xu, Guofeng Xu, Xiaoliang Fang, Lei He |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Proteomics Pathology medicine.medical_specialty Cytoskeleton organization Proteome Clinical Biochemistry Hydronephrosis medicine.disease_cause Extracellular matrix 03 medical and health sciences Western blot Medicine Humans 030102 biochemistry & molecular biology medicine.diagnostic_test business.industry Biglycan Infant Extracellular Matrix Oxidative Stress 030104 developmental biology Female Ureter business Oxidative stress Biomarkers Extracellular matrix organization Ureteral Obstruction |
| Zdroj: | Proteomics. Clinical applications. 14(6) |
| ISSN: | 1862-8354 |
| Popis: | 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, the stenotic ureter proteome of UPJO in infants is compared with their own normal pre-stenotic segments. Experimental design Data independent acquisition-based proteomics are performed to compare proteome between pre-stenotic and stenotic ureter from nine UPJO infants. Gene ontology analysis, hierarchical cluster analysis, and network interaction are performed to characterize biological functions of significantly altered proteins. Selected significantly altered proteins are validated by western blot on another three UPJO infants. Results 15 proteins are up-regulated and 33 proteins are down-regulated during stenotic pathology. Significantly altered proteins are 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 are validated providing possible mechanism in UPJO which could be associated impaired smooth muscle cell, epithelial integrity, and increased oxidative stress. CONCLUSIONS AND CLINICAL RELEVANCE: This 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. |
| Databáze: | OpenAIRE |
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