期刊
EXPERIMENTAL CELL RESEARCH
卷 317, 期 7, 页码 932-940出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2011.01.025
关键词
PI3K/Akt pathway; Apoptosis; LY294002; NF-kappa B; PKHD1
资金
- Shenzhen Science and Technology Plan [200802092]
- PKD Foundation
- National Institutes of Health [P50DK074030]
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 kappa B (NF-kappa B) in FPC knockdown kidney cells. We show that PIGLID1-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-kappa B 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-kappa B activity. These observations provide a potential platform for determining FPC function and therapeutic investigation of ARPKD. (C) 2011 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据