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Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
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Published on: September 1, 2015

Activation of the AKT/mTOR pathway in autosomal recessive polycystic kidney disease (ARPKD)

Dagmar-Christiane Fischer1, Ulrike Jacoby, Lars Pape

  • 1Department of Pediatrics, University of Rostock, Germany. dagmar-christiane.fischer@med.uni-rostock.de

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|January 30, 2009
PubMed

Insights

Autosomal recessive polycystic kidney disease (ARPKD) involves dysregulated fibrocystin/polyductin (FPC) expression and activated AKT/mTOR signaling in kidney cysts. Further research into mTOR inhibitors may offer therapeutic potential for ARPKD patients.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Genetics

Background:

  • Autosomal recessive polycystic kidney disease (ARPKD) is a congenital hepatorenal fibrocystic syndrome.
  • It is caused by mutations in the PKHD1 gene, encoding fibrocystin/polyductin (FPC).
  • The role of mammalian target of rapamycin (mTOR) signaling in ARPKD progression is unknown.

Purpose of the Study:

  • To investigate the role of mTOR signaling in ARPKD.
  • To examine FPC expression and AKT/mTOR pathway activation in ARPKD kidney tissues.

Main Methods:

  • Immunohistochemical analysis of FPC, Ki-67, phosphorylated AKT, mTOR, and S6K in kidney specimens from ARPKD patients (n=12) and controls (n=4).
  • PKHD1 mutation analysis was performed for all patients.
  • Antibodies targeting activated isoforms of AKT, mTOR, and S6K were used.

Main Results:

  • PKHD1 mutations were confirmed in 10/12 patients.
  • Dysregulated FPC expression was observed in ARPKD kidneys compared to controls.
  • Activated AKT, mTOR, and S6K were strongly expressed in cystic epithelia of ARPKD kidneys, but not associated with proliferation (Ki-67).

Conclusions:

  • AKT/mTOR signaling plays a central role in ARPKD.
  • Further research is warranted to explore mTOR inhibitors as a potential therapy for ARPKD.
Abstract

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