Comprehensive proteomic quantification of bladder stone progression in a cystinuric mouse model using data-independent acquisitions

Cystinuria is one of various disorders that cause biomineralization in the urinary system, including bladder stone formation in humans. It is most prevalent in children and adolescents and more aggressive in males. There is no cure, and only limited disease management techniques help to solubilize t...

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Published in:PloS one Vol. 17; no. 6; p. e0250137
Main Authors: Rose, Jacob, Basisty, Nathan, Zee, Tiffany, Wehrfritz, Cameron, Bose, Neelanjan, Desprez, Pierre-Yves, Kapahi, Pankaj, Stoller, Marshall, Schilling, Birgit
Format: Journal Article
Language:English
Published: United States Public Library of Science 30.06.2022
Public Library of Science (PLoS)
Subjects:
Acids
Aminoaciduria, Renal
Analysis
Animals
Biology and Life Sciences
Bladder
Children
Coagulation
Computed tomography
Cystine - metabolism
Cystinuria
Data acquisition
Degranulation
Depth profiling
Developmental stages
Diagnosis
Genetic aspects
Male
Mass spectrometry
Medicine and Health Sciences
Mice
Mineralization
Peptides
Proteins
Proteomes
Proteomics
Research and Analysis Methods
Ribosomal proteins
Scientific imaging
Solvents
Urinary Bladder Calculi - diagnostic imaging
Urine
X-Ray Microtomography
United States
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Cystinuria is one of various disorders that cause biomineralization in the urinary system, including bladder stone formation in humans. It is most prevalent in children and adolescents and more aggressive in males. There is no cure, and only limited disease management techniques help to solubilize the stones. Recurrence, even after treatment, occurs frequently. Other than a buildup of cystine, little is known about factors involved in the formation, expansion, and recurrence of these stones. This study sought to define the growth of bladder stones, guided by micro-computed tomography imaging, and to profile dynamic stone proteome changes in a cystinuria mouse model. After bladder stones developed in vivo , they were harvested and separated into four developmental stages (sand, small, medium and large stone), based on their size. Data-dependent and data-independent acquisitions allowed deep profiling of stone proteomics. The proteomic signatures and pathways illustrated major changes as the stones grew. Stones initiate from a small nidus, grow outward, and show major enrichment in ribosomal proteins and factors related to coagulation and platelet degranulation, suggesting a major dysregulation in specific pathways that can be targeted for new therapeutic options.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0250137