Down-regulation of PKHD1 induces cell apoptosis through PI3K and NF-κB pathways

Liping Sun, Shixuan Wang, Chaofeng Hu, Xinzhou Zhang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Mutations in PKHD1 (polycystic kidney and hepatic disease gene 1) gene cause the autosomal recessive polycystic kidney disease (ARPKD). Fibrocystin/polyductin (FPC), encoded by PKHD1, is a membrane-associated receptor-like protein. Although it is widely accepted that cystogenesis is mostly due to aberrant cell proliferation and apoptosis, it is still unclear how apoptosis is regulated. The aim of this study is to analyze the relationship among apoptosis, phosphatidylinositol 3-kinase (PI3K)/Akt and nuclear factor κB (NF-κB) in FPC knockdown kidney cells. We show that PKHD1-silenced HEK293 cells demonstrate a higher PI3K/Akt activity. Selective inhibition of PI3K/Akt using LY294002 or wortmannin in these cells increases serum starvation-induced HEK293 cell apoptosis with a concomitant decrease in cell proliferation and higher caspase-3 activity. PI3K/Akt inhibition also leads to increased NF-κB activity in these cells. We conclude that the PI3K/Akt pathway is involved in apoptotic function in PKHD1-silenced cells, and PI3K/Akt inhibition correlates with upregulation of NF-κB activity. These observations provide a potential platform for determining FPC function and therapeutic investigation of ARPKD.

Original languageEnglish (US)
Pages (from-to)932-940
Number of pages9
JournalExperimental Cell Research
Volume317
Issue number7
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Fingerprint

Autosomal Recessive Polycystic Kidney
Phosphatidylinositol 3-Kinase
Down-Regulation
Apoptosis
Genes
HEK293 Cells
Cell Proliferation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Starvation
Caspase 3
Up-Regulation
Kidney
Mutation
Membranes
Serum

Keywords

  • Apoptosis
  • LY294002
  • NF-κB
  • PI3K/Akt pathway
  • PKHD1\

ASJC Scopus subject areas

  • Cell Biology

Cite this

Down-regulation of PKHD1 induces cell apoptosis through PI3K and NF-κB pathways. / Sun, Liping; Wang, Shixuan; Hu, Chaofeng; Zhang, Xinzhou.

In: Experimental Cell Research, Vol. 317, No. 7, 01.01.2011, p. 932-940.

Research output: Contribution to journalArticle

Sun, Liping ; Wang, Shixuan ; Hu, Chaofeng ; Zhang, Xinzhou. / Down-regulation of PKHD1 induces cell apoptosis through PI3K and NF-κB pathways. In: Experimental Cell Research. 2011 ; Vol. 317, No. 7. pp. 932-940.
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