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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Vydané v:	PloS one Ročník 17; číslo 6; s. e0250137
Hlavní autori:	Rose, Jacob, Basisty, Nathan, Zee, Tiffany, Wehrfritz, Cameron, Bose, Neelanjan, Desprez, Pierre-Yves, Kapahi, Pankaj, Stoller, Marshall, Schilling, Birgit
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 30.06.2022 Public Library of Science (PLoS)
Predmet:	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
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0250137