title: Podocyte proteins in congenital and minimal change nephrotic syndrome.
abstract: BACKGROUND
  Podocyte foot process effacement is a uniform finding in kidneys with heavy proteinuria. Its molecular mechanisms, however, are unsolved. We analyzed the expression of podocyte proteins in two kidney disorders: Congenital nephrotic syndrome of the Finnish type (CNF) and minimal change nephrotic syndrome (MCNS).
  
  
  METHODS
  Immunoperoxidase and immunofluorescence stainings were used to semiquantitatively analyze the expression of 13 and 4 podocyte proteins from different cellular compartments in CNF and MCNS, respectively.
  
  
  RESULTS
  The expression of a major slit diaphragm (SD) protein, Neph 1, showed a 46-fold decrease (p < 0.0001) in CNF kidneys as compared to controls. The three cytosolic adaptor proteins, podocin, NCK1/2, CD2AP, connecting SD proteins to the actin cytoskeleton were slightly upregulated (1.1-fold, 1.4-fold, and 3.3-fold, respectively). Also, the staining of the two actin-regulator proteins, ACTN4 and INF2, was modestly increased (2.2-fold and 1.7-fold, respectively, p < 0.0001). Staining for α3-integrin showed 1.9-fold increase (p < 0.0001) indicating that the major podocyte anchoring complex, α3β1, was well preserved in CNF glomeruli. In contrast to CNF kidneys, Neph1 FAT1, ACTN4, and CD2AP were quite normally expressed in proteinuric and non-proteinuric MCNS kidneys.
  
  
  CONCLUSIONS
  CNF kidneys lacking nephrin show decreased expression of other SD proteins but not cytosolic podocyte proteins involved in the foot process architecture or function. In MCNS kidneys, these changes in expression were not observed.
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Tukholmankatu 8, 00290, Helsinki, Finland. maija.suvanto@helsinki.fi.
authors.forename: Maija
authors.initials: M
authors.lastname: Suvanto
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Tukholmankatu 8, 00290, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Jahnukainen
authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Kestilä
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Tukholmankatu 8, 00290, Helsinki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Jalanko
mesh_terms: D000185:Actinin / Q000032:analysis; D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000328:Adult; D015820:Cadherins / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis; D000080865:Formins; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D039422:Integrin alpha3 / Q000032:analysis; D039201:Integrin alpha3beta1 / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D008840:Microfilament Proteins / Q000032:analysis; D009402:Nephrosis, Lipoid / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000378:metabolism*; D050199:Podocytes / Q000737:chemistry*
chemical_list: C111453:ACTN4 protein, human; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D015820:Cadherins; D003598:Cytoskeletal Proteins; C502403:FAT1 protein, human; D000080865:Formins; C546959:INF2 protein, human; D039422:Integrin alpha3; D039201:Integrin alpha3beta1; D047908:Intracellular Signaling Peptides and Proteins; C431137:KIRREL1 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; D000185:Actinin
keywords: Actin cytoskeleton; CNF; MCNS; Neph1; Nephrin; Podocyte