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

Apoptosis : an International Journal on Programmed Cell Death
Alessandra MangoliniLaura del Senno

Abstract

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-kappaB, a transcription factor which reduces apoptosis in many organs and tissues. Interestingly, selective inactivation of NF-kappaB using either an NF-kappaB decoy or parthenolide, a blocker of IKK-dependent NF-kappaB activation, reduced, rather then in...Continue Reading

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Citations

Mar 17, 2015·Molecular Immunology·Huan ZhangLiurong Fang
Jan 19, 2011·Biochimica Et Biophysica Acta·Béatrice Goilav
Jul 28, 2016·World Journal of Nephrology·Michelle H T TaGopala K Rangan
Apr 23, 2020·Cellular Signalling·Chiara Formica, Dorien J M Peters

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis