Proteomic analysis identifies insulin-like growth factor-binding protein-related protein-1 as a podocyte product.
The podocyte secretory proteome may influence the phenotype of adjacent podocytes, endothelial cells, parietal epithelial cells, and tubular epithelial cells but has not been systematically characterized. We have initiated studies to characterize this proteome, with the goal of further understanding the podocyte cell biology. We cultured differentiated conditionally immortalized human podocytes and subjected the proteins in conditioned medium to mass spectrometry. At a false discovery rate of <3%, we identified 111 candidates from conditioned medium, including 44 proteins that have signal peptides or are described as secreted proteins in the UniProt database. As validation, we confirmed that one of these proteins, insulin-like growth factor-binding protein-related protein-1 (IGFBP-rP1), was expressed in mRNA and protein of cultured podocytes. In addition, transforming growth factor-β1 stimulation increased IGFBP-rP1 in conditioned medium. We analyzed IGFBP-rP1 glomerular expression in a mouse model of human immunodeficiency virus-associated nephropathy. IGFBP-rP1 was absent from podocytes of normal mice and was expressed in podocytes and pseudocrescents of transgenic mice, where it was coexpressed with desmin, a podocyte injury marker. We conclude that IGFBP-rP1 may be a product of injured podocytes. Further analysis of the podocyte secretory proteome may identify biomarkers of podocyte injury.
Matsumoto
Takayuki
T
Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
Hess
Sonja
S
Kajiyama
Hiroshi
H
Sakairi
Toru
T
Saleem
Moin A
MA
Mathieson
Peter W
PW
Nojima
Yoshihisa
Y
Kopp
Jeffrey B
JB
D016263:AIDS-Associated Nephropathy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism; D004195:Disease Models, Animal; D016334:Genes, vpr / Q000235:genetics; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D040901:Proteomics
D003893:Desmin; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1