PURPOSE: Among the different types of kidney stones, matrix stones are uncommon urinary calculi composed of a soft, pliable, amorphous substance with little crystalline content. To gain insight into the pathogenesis we investigated the protein component by analyzing the proteomic profiles of surgically removed matrix stones. MATERIALS AND METHODS: A total of 5 stones were harvested from 4 patients who underwent surgery for medical reasons at 3 clinical centers during a 7-year period. Matrix stone proteome characterization was performed by mass spectrometry based techniques using an integrated top-down/bottom-up proteomic platform. RESULTS: We identified 142 nonredundant proteins and peptides across all samples. Neutrophil defensin 1, and proteins S100-A8 and S100-A9 were the main components of these renal calculi. CONCLUSIONS: The abundance of identified inflammatory molecules points to an inflammatory process as the event that initializes soft calculi formation rather than as a consequence of such formation. The post-translational oxidative changes in S100-A8 and A9, and the presence of thymosin β-4, granulins and ubiquitin also suggest the intervention of host defenses through a superimposed, vigorous counter inflammatory process. The post-translational changes seen in the proteins and peptides, and the known self-assembling capability of S100-A8 and S100-A9 probably explain the gelatinous consistency of these stones.

Martelli, C., Marzano, V., Iavarone, F., Huang, L., Vincenzoni, F., Desiderio, C., Messana, I., Beltrami, P., Zattoni, F., Ferraro, P. M., Buchholz, N., Locci, G., Faa, G., Castagnola, M., Gambaro, G., Characterization of the Protein Components of Matrix Stones Sheds Light on S100-A8 and S100-A9 Relevance in the Inflammatory Pathogenesis of These Rare Renal Calculi, <<THE JOURNAL OF UROLOGY>>, 2016; 196 (3): 911-918. [doi:10.1016/j.juro.2016.04.064] [http://hdl.handle.net/10807/83288]

Characterization of the Protein Components of Matrix Stones Sheds Light on S100-A8 and S100-A9 Relevance in the Inflammatory Pathogenesis of These Rare Renal Calculi

Martelli, Claudia;Marzano, Valeria;Iavarone, Federica;Huang, Liling;Desiderio, Claudia;Messana, Irene;Ferraro, Pietro Manuel;Castagnola, Massimo;Gambaro, Giovanni
2016

Abstract

PURPOSE: Among the different types of kidney stones, matrix stones are uncommon urinary calculi composed of a soft, pliable, amorphous substance with little crystalline content. To gain insight into the pathogenesis we investigated the protein component by analyzing the proteomic profiles of surgically removed matrix stones. MATERIALS AND METHODS: A total of 5 stones were harvested from 4 patients who underwent surgery for medical reasons at 3 clinical centers during a 7-year period. Matrix stone proteome characterization was performed by mass spectrometry based techniques using an integrated top-down/bottom-up proteomic platform. RESULTS: We identified 142 nonredundant proteins and peptides across all samples. Neutrophil defensin 1, and proteins S100-A8 and S100-A9 were the main components of these renal calculi. CONCLUSIONS: The abundance of identified inflammatory molecules points to an inflammatory process as the event that initializes soft calculi formation rather than as a consequence of such formation. The post-translational oxidative changes in S100-A8 and A9, and the presence of thymosin β-4, granulins and ubiquitin also suggest the intervention of host defenses through a superimposed, vigorous counter inflammatory process. The post-translational changes seen in the proteins and peptides, and the known self-assembling capability of S100-A8 and S100-A9 probably explain the gelatinous consistency of these stones.
eng
Martelli, C., Marzano, V., Iavarone, F., Huang, L., Vincenzoni, F., Desiderio, C., Messana, I., Beltrami, P., Zattoni, F., Ferraro, P. M., Buchholz, N., Locci, G., Faa, G., Castagnola, M., Gambaro, G., Characterization of the Protein Components of Matrix Stones Sheds Light on S100-A8 and S100-A9 Relevance in the Inflammatory Pathogenesis of These Rare Renal Calculi, <>, 2016; 196 (3): 911-918. [doi:10.1016/j.juro.2016.04.064] [http://hdl.handle.net/10807/83288]
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