NDT Advance Access originally published online on September 19, 2007
Nephrology Dialysis Transplantation 2008 23(1):176-185; doi:10.1093/ndt/gfm587
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Urinary proteome and potential biomarkers associated with serial pathogenesis steps of focal segmental glomerulosclerosis
1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 2Department of Nursing, Chang-Gung Institute of Technology, Taoyuan, 3Department of Pathology, Tri-Service General Hospital, 4Graduate Institute of Life Sciences and 5Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Correspondence to: Dr Hao-Ai Shui, Graduate Institute of Medical Sciences, National Defense Medical Center, 161, Min-Chuan East Road, 6th Section, Taipei, Taiwan (114), ROC. Email: haoai{at}ndmctsgh.edu.tw
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Abstract |
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Background. Focal segmental glomerulosclerosis (FSGS) is a chronic nephropathy showing characteristic glomerular sclerosis. So far, the diagnosis and prognosis of FSGS rely mainly on the invasive biopsy. Searching for potential FSGS-associated urinary biomarkers representing pre-sclerotic and serial sclerotic stages of FSGS could be helpful to the non-invasive diagnosis and prognosis of FSGS.
Methods. In the present study, we used a 2D gel-based proteomic approach to identify urinary proteins at pre-sclerotic and different sclerotic stages of an FSGS mouse model in order to find FSGS-related urinary proteins. The FSGS mouse model was established in Balb/c mice by a single injection of adriamycin, and disease severity was monitored by renal biological parameters and histopathological features. Urine was collected on days 0, 4, 7, 11, 15 and 20, and subjected to two-dimensional electrophoresis (2-DE) analysis. Proteins were identified by matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) and a protein database search. Some of the identified proteins were confirmed by western blot analysis.
Results. We identified 37 urinary proteins showing characteristic patterns of dynamic changes along the disease course of FSGS. Early urinary proteins appearing before glomerular scleoris were noticed. Importantly, 11 urine proteins are novel to FSGS and have known functions highly associated with different pathogenetic steps of the disease, including haemodynamic disturbance, podocyte apoptosis, ECM-protein deposition and glomerular sclerosis.
Conclusions. Some urinary proteins appearing earlier than glomerular sclerosis could serve as potential early diagnostic biomarkers. The proteins with the pathogenic roles could serve as potential non-invasive prognostic markers of FSGS, and give an insight into pathogenic mechanisms of this sclerosis disease.
Keywords: diagnosis; focal segmental glomerulosclerosis; potential urinary biomarkers; prognosis; proteomics
Received for publication: 23. 5.07
Accepted in revised form: 30. 7.07
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