NF-κB activation is required for apoptosis in fibrocystin/polyductin- depleted kidney epithelial cells

Alessandra Mangolini, Marco Bogo, Chiara Durante, Monica Borgatti, Roberto Gambari, Peter C. Harris, Rosario Rizzuto, Paolo Pinton, Gianluca Aguiari, Laura Del Senno

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in PKHD1, a gene encoding fibrocystin/polyductin (FC1), a membrane-associated receptor-like protein involved in the regulation of tubular cell adhesion, proliferation and apoptosis. Although it is generally accepted that apoptosis is implicated in ARPKD, the question of whether increased apoptosis is a normal response to abnormal cell proliferation or, instead, it is a primary event, is still subject to debate. In support of the latter hypothesis, we hereby provide evidence that apoptosis occurs in the absence of hyper-proliferation of FC1-depleted kidney cells. In fact, a decrease in cell proliferation, with a concomitant increase in apoptotic index and caspase-3 activity was observed in response to FC1-depletion by PKHD1 siRNA silencing in HEK293 and 4/5 tubular cells. FC1-depletion also induced reduction in ERK1/2 kinase activation, upregulation of the pro-apoptotic protein p53 and activation of NF-κB, a transcription factor which reduces apoptosis in many organs and tissues. Interestingly, selective inactivation of NF-κB using either an NF-κB decoy or parthenolide, a blocker of IKK-dependent NF-κB activation, reduced, rather then increased, apoptosis and p53 levels in FC1-depleted cells. Therefore, the proapoptotic function of NF-κB during cell death by FC1-depletion in kidney cells is evident.

Original languageEnglish (US)
Pages (from-to)94-104
Number of pages11
Issue number1
StatePublished - Jan 2010


  • Apoptosis
  • Autosomal recessive polycystic kidney disease (ARPKD)
  • Fibrocystin
  • Kidney cells
  • NF-κB inhibitors

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research


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