Claudia Martelli1, Valeria Marzano1, Federica Iavarone1, Liling Huang1, Federica Vincenzoni1, Claudia Desiderio2, Irene Messana3, Paolo Beltrami4, Filiberto Zattoni4, Pietro Manuel Ferraro5, Noor Buchholz6, Giorgia Locci7, Gavino Faa7, Massimo Castagnola8, Giovanni Gambaro9. 1. Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy. 2. Institute of Chemistry of Molecular Recognition, Italian National Research Council, Rome, Italy. 3. Department of Life and Environmental Sciences, Cagliari University, Cagliari, Italy. 4. Urology Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy. 5. Nephrology Division, Institute of Internal Medicine, Catholic University, Rome, Italy. 6. U-merge (Urology in Emerging Countries), London, United Kingdom. 7. Pathology Division, Department of Surgery, Cagliari University, Cagliari, Italy. 8. Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy; Institute of Chemistry of Molecular Recognition, Italian National Research Council, Rome, Italy. 9. Nephrology Division, Institute of Internal Medicine, Catholic University, Rome, Italy. Electronic address: giovanni.gambaro@unicatt.it.
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.
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.
Authors: Jules R Stephan; Fangting Yu; Rebekah M Costello; Benjamin S Bleier; Elizabeth M Nolan Journal: J Am Chem Soc Date: 2018-12-05 Impact factor: 15.419