title: Inflammatory and fibrotic proteins proteomically identified as key protein constituents in urine and stone matrix of patients with kidney calculi.
abstract: To uncover whether urinary proteins are incorporated into stones, the proteomic profiles of kidney stones and urine collected from the same patients have to be explored. We employed 1D-PAGE and nanoHPLC-ESI-MS/MS to analyze the proteomes of kidney stone matrix (n=16), nephrolithiatic urine (n=14) and healthy urine (n=3). We identified 62, 66 and 22 proteins in stone matrix, nephrolithiatic urine and healthy urine, respectively. Inflammation- and fibrosis-associated proteins were frequently detected in the stone matrix and nephrolithiatic urine. Eighteen proteins were exclusively found in the stone matrix and nephrolithiatic urine, considered as candidate biomarkers for kidney stone formation. S100A8 and fibronectin, representatives of inflammation and fibrosis, respectively, were up-regulated in nephrolithiasis renal tissues. S100A8 was strongly expressed in infiltrated leukocytes. Fibronectin was over-expressed in renal tubular cells. S100A8 and fibronectin were immunologically confirmed to exist in nephrolithiatic urine and stone matrix, but in healthy urine they were undetectable. Conclusion, both kidney stones and urine obtained from the same patients greatly contained inflammatory and fibrotic proteins. S100A8 and fibronectin were up-regulated in stone-baring kidneys and nephrolithiatic urine. Therefore, inflammation and fibrosis are suggested to be involved in the formation of kidney calculi.
authors: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330 Thailand. Electronic address: chanchai.b@chula.ac.th.
authors: Chanchai
authors: C
authors: Boonla
authors: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330 Thailand.
authors: Piyaratana
authors: P
authors: Tosukhowong
authors: Department of Molecular Embryology, Institute for Anatomy and Cell Biology, University of Freiburg, 79104 Freiburg, Germany.
authors: Björn
authors: B
authors: Spittau
authors: Center for Biological Systems Analysis (ZBSA), Core Facility Proteomics, University of Freiburg, 79104 Freiburg, Germany.
authors: Andreas
authors: A
authors: Schlosser
authors: Division of Urological Surgery, Khon Kaen Hospital, Khon Kaen 40000 Thailand.
authors: Chaowat
authors: C
authors: Pimratana
authors: Department of Molecular Embryology, Institute for Anatomy and Cell Biology, University of Freiburg, 79104 Freiburg, Germany. Electronic address: kerstin.krieglstein@anat.uni-freiburg.de.
authors: Kerstin
authors: K
authors: Krieglstein
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007669:Kidney Calculi / Q000378:metabolism* / Q000473:pathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D040901:Proteomics
chemical_list: D015415:Biomarkers
keywords: Fibronectin; Fibrosis; Inflammation; Kidney stone; Proteomics; S100A8