Hsf-1 affects podocyte markers NPHS1, NPHS2 and WT1 in a transgenic mouse model of TTRVal30Met-related amyloidosis

Ioannis Petrakis, Vasiliki Mavroeidi, Kostas Stylianou, Eva Andronikidi, Eirini Lioudaki, Kostas Perakis, Spyridon Stratigis, Eleftheria Vardaki, Maria Zafeiri, Kostantinos Giannakakis, Andreas Plaitakis, George Amoiridis, Maria Joao Saraiva, Eugene Daphnis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Introduction: 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. Materials and 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.

Original languageEnglish
Pages (from-to)164-172
Number of pages9
JournalAmyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
Volume20
Issue number3
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • ATTR
  • GBM
  • Hsf-1
  • Nephrin
  • Podocin
  • Podocytes

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