Proteomic analysis of renal calculi indicates an important role for inflammatory processes in calcium stone formation.
Even though renal stones/calculi occur in approximately 10% of individuals, they are an enormous economic burden to the entire US health system. While the relative metabolic composition of renal calculi is generally known, there is no clear understanding of the genetics of renal stone formation, nor are there clear prognostic indicators of renal stone formation. The application of proteomics to the analysis of renal calculi axiomatically holds that insight into renal stone pathobiology can be gained by a more comprehensive understanding of renal calculus protein composition. We analyzed isolated renal stone matrix proteins with mass spectrometric and immunohistochemical methods identifying 158 proteins with high confidence, including 28 common proteins. The abundant proteins included those identified previously in stones and proteins identified here for the first time, such as myeloid lineage-specific, integral membrane and lipid regulatory proteins. Pathway analyses of all proteins identified suggested that a significant fraction of the most abundant matrix proteins participate in inflammatory processes. These proteomic results support the hypothesis that stone formation induces a cellular inflammatory response and the protein components of this response contribute to the abundant stone matrix proteome.
Merchant
Michael L
ML
Department of Medicine, James Graham Brown Cancer Center, University of Louiville, Rm. 102S, Donald Baxter Research Bldg., 570 S. Preston St., Louisville, KY 40202, USA. mlmerc02@gwise.louisville.edu
Cummins
Timothy D
TD
Wilkey
Daniel W
DW
Salyer
Sarah A
SA
Powell
David W
DW
Klein
Jon B
JB
Lederer
Eleanor D
ED
D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000032:analysis; D008297:Male; D053495:Osteopontin / Q000032:analysis; D011379:Prognosis; D040901:Proteomics / Q000379:methods* / Q000592:standards*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014545:Urinary Calculi / Q000737:chemistry* / Q000209:etiology / Q000276:immunology*
D016326:Extracellular Matrix Proteins; D008074:Lipoproteins; D053495:Osteopontin