Proteomics

Dataset Information

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Identification of biomarkers for PKD1 using urinary exosomes


ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of ESRD. Affected individuals inherit a defective copy of either the PKD1 or PKD2 gene, encoding the proteins polycystin?1 (PC1) or polycystin?2 (PC2) respectively. PC1 and PC2 are secreted on urinary exosome?like vesicles (ELVs) (100nm diameter vesicles), where PC1 is present in a cleaved form and may be complexed with PC2. Label free quantitative proteomic studies of urine ELVs in an initial discovery cohort (13 PKD1 and 18 Normals), revealed that of 2008 ELV proteins, nine (0.32%) showed a statistically significant difference between PKD1 and normals at a p<0.025. PC1 was reduced to 54% of the normal level (p<0.02) and PC2 reduced to 53% (p<0.001). TMEM2, a protein with homology to fibrocystin, the product of the polycystic hepatic and kidney disease (PKHD1) gene, is increased 2.1 fold (p<0.025). The PC1/TMEM2 ratio correlated inversely with height adjusted total kidney volume (HtTKV) in the discovery cohort and the ratio of PC1/TMEM2 or PC2/TMEM2 could be used to distinguish PKD1 from normals in a confirmation cohort. In summary, this study suggests that a test based on the urine exosomal PC1/TMEM2 or PC2/TMEM2 ratio may have utility in the diagnosis and perhaps monitoring of PKD1.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine, Kidney Glomerular Epithelial Cell

DISEASE(S): Polycystic Kidney Disease

SUBMITTER: Roman Zenka  

LAB HEAD: Daniel McCormick

PROVIDER: PXD001075 | Pride | 2014-12-02

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
o63_11dec04_01_35_enoang20fm1.RAW Raw
o63_11dec04_02_35_trail_myeast1.RAW Raw
o63_11dec04_03_35min_11elv_bf25.RAW Raw
o63_11dec04_04_35min_blank1.RAW Raw
o63_11dec04_05_11elv_bfyeast01.RAW Raw
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Publications


Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of ESRD. Affected individuals inherit a defective copy of either PKD1 or PKD2, which encode polycystin-1 (PC1) or polycystin-2 (PC2), respectively. PC1 and PC2 are secreted on urinary exosome-like vesicles (ELVs) (100-nm diameter vesicles), in which PC1 is present in a cleaved form and may be complexed with PC2. Here, label-free quantitative proteomic studies of urine ELVs in an initial discovery cohort (13 individuals with P  ...[more]

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