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Selective protein enrichment in calcium oxalate stone matrix: a window to pathogenesis? Urolithiasis 2019 Dec;47(6):521-532

Date

04/18/2019

Pubmed ID

30993355

Pubmed Central ID

PMC8496971

DOI

10.1007/s00240-019-01131-3

Scopus ID

2-s2.0-85064686878 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Urine proteins are thought to control calcium oxalate stone formation, but over 1000 proteins have been reported in stone matrix obscuring their relative importance. Proteins critical to stone formation should be present at increased relative abundance in stone matrix compared to urine, so quantitative protein distribution data were obtained for stone matrix compared to prior urine proteome data. Matrix proteins were isolated from eight stones (> 90% calcium oxalate content) by crystal dissolution and further purified by ultradiafiltration (> 10 kDa membrane). Proteomic analyses were performed using label-free spectral counting tandem mass spectrometry, followed by stringent filtering. The average matrix proteome was compared to the average urine proteome observed in random urine samples from 25 calcium oxalate stone formers reported previously. Five proteins were prominently enriched in matrix, accounting for a mass fraction of > 30% of matrix protein, but only 3% of urine protein. Many highly abundant urinary proteins, like albumin and uromodulin, were present in matrix at reduced relative abundance compared to urine, likely indicating non-selective inclusion in matrix. Furthermore, grouping proteins by isoelectric point demonstrated that the stone matrix proteome was highly enriched in both strongly anionic (i.e., osteopontin) and strongly cationic (i.e., histone) proteins, most of which are normally found in intracellular or nuclear compartments. The fact that highly anionic and highly cationic proteins aggregate at low concentrations and these aggregates can induce crystal aggregation suggests that protein aggregation may facilitate calcium oxalate stone formation, while cell injury processes are implicated by the presence of many intracellular proteins.

Author List

Wesson JA, Kolbach-Mandel AM, Hoffmann BR, Davis C, Mandel NS

Authors

Carley Davis MD Professor in the Urologic Surgery department at Medical College of Wisconsin
Jeffrey A. Wesson MD, PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Calcium Oxalate
Crystallization
Humans
Kidney Calculi
Proteome
Urinary Calculi