title: Hsf-1 affects podocyte markers NPHS1, NPHS2 and WT1 in a transgenic mouse model of TTRVal30Met-related amyloidosis.
abstract: BACKGROUND
  Familial amyloid polyneuropathy is characterized by transthyretin (TTR) deposition in various tissues, including the kidneys. While deposition induces organ dysfunction, renal involvement in TTR-related amyloidosis could manifest from proteinuria to end-stage kidney failure. As proteinuria is considered result of glomerular filtration barrier injury we investigated whether TTR deposition affects either glomerular basement membrane (GBM) or podocytes.
  
  
  METHODS
  Immunohistochemistry, immunoblot and gene expression studies for nephrin, podocin and WT1 were run on renal tissue from human-TTRV30M transgenic mice hemizygous or homozygous for heat shock factor one (Hsf-1). Transmission electron microscopy was used for evaluation of podocyte foot process width (PFW) and GBM thickness in Hsf-1 hemizygous mice with or without TTRV30M or amyloid deposition.
  
  
  RESULTS
  Glomeruli of hsf-1 hemizygous transgenic mice showed lower nephrin and podocin protein levels but an increased podocyte number when compared to Hsf-1 homozygous transgenic mice. Nephrin, podocin and WT1 gene expression levels were unaffected by the Hsf-1 carrier status. TTRV30M deposition was associated with increased PFW and GBM thickness.
  
  
  CONCLUSIONS
  Under the effect of Hsf-1 hemizygosity, TTRV30M deposition has deleterious effects on GBM thickness, PFW and slit diaphragm composition, without affecting nephrin and podocin gene expression.
authors.affiliation: Department of Nephrology, University of Crete, Greece. petrakgia@gmail.com
authors.forename: Ioannis
authors.initials: I
authors.lastname: Petrakis
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Mavroeidi
authors.forename: Kostas
authors.initials: K
authors.lastname: Stylianou
authors.forename: Eva
authors.initials: E
authors.lastname: Andronikidi
authors.forename: Eirini
authors.initials: E
authors.lastname: Lioudaki
authors.forename: Kostas
authors.initials: K
authors.lastname: Perakis
authors.forename: Spyridon
authors.initials: S
authors.lastname: Stratigis
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Vardaki
authors.forename: Maria
authors.initials: M
authors.lastname: Zafeiri
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Giannakakis
authors.forename: Andreas
authors.initials: A
authors.lastname: Plaitakis
authors.forename: George
authors.initials: G
authors.lastname: Amoiridis
authors.forename: Maria Joao
authors.initials: MJ
authors.lastname: Saraiva
authors.forename: Eugene
authors.initials: E
authors.lastname: Daphnis
mesh_terms: D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000473:pathology; D000076249:Heat Shock Transcription Factors; D057898:Hemizygote; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000682:Amyloid; D015415:Biomarkers; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D011228:Prealbumin; D014157:Transcription Factors; D025721:WT1 Proteins; C113267:nephrin; C041120:amyloid prealbumin