Characterization of plasma factors that alter the permeability to albumin within isolated glomeruli

Luca Musante, Giovanni Candiano, Maurizio Bruschi, Cristina Zennaro, Michele Carraro, Mary Artero, Maria Gabriella Giuffrida, Amedeo Conti, Annalisa Santucci, Gian Marco Ghiggeri

Research output: Contribution to journalArticle

Abstract

Focal segmental glomerulosclerosis (FSGS) is responsible for intractable proteinuria and has become the leading cause of renal insufficiency in children. Protenuria in FSGS is probably due to the effect of one or more permeability plasma factors which increase the glomerular permeability to proteins. We fractioned serum from children with FSGS using two mixed chromatographic-electrophoretic approaches and have purified ten proteins among several hundreds which maintained the original permeability activity after renaturation, utilizing an isolated rat glomeruli assay. Six proteins were successfully characterized by mass spectometry as fibulin, apolipoprotein J, vitronectin, albumin isoforms, γ chain fibrinogen and mannan-binding lectin-associated serine protease. Both procedures utilized for purification were based on affinity chromatography with Protein A-Sepharose and ended with two-dimensional electrophoresis, whereas the intermediate steps were different. Cross inhibition with zinc and aprotinin of purified factors and whole FSGS serum indicate strong homology. These are the first data demonstrating permeability activity for serum proteins, an observation with important implications in pathogenesis of proteinuria. Determination of the serum levels of each protein and a careful differentiation of FSGS from normal serum could provide the basis for clarifying the mechanism of proteinuria.

Original languageEnglish
Pages (from-to)197-205
Number of pages9
JournalProteomics
Volume2
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Glomerulosclerosis
  • Permeability factor
  • Proteinuria
  • Renal transplantation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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