PI3K-AKT pathway mediates growth and survival signals during development of fetal mouse lung
PI3K-AKT pathway mediates growth and survival signals during development of fetal mouse lung
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DOI：
10.1016/j.tice.2004.09.002
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发表时间：
2005-02-01
期刊：
影响因子：
2.6
通讯作者：
Kitamura, H
中科院分区：
文献类型：
--
作者：
Wang, J;Ito, T;Kitamura, H
我们研究了PI3K-AKT信号通路在胎肺发育中的作用。Western blotting显示，磷酸化AKT(PACT)在胎龄12天和14天高表达，之后表达减弱。免疫组织化学检测，PACK主要表达于胎龄早期的呼吸道上皮细胞。我们观察了成纤维细胞生长因子1(FGF1)、PI3K抑制剂(LY294002和Wortmannin)、MAPK抑制剂(PD98059)以及FGF1和每种抑制剂对肺形态发生、BrdU掺入和细胞凋亡的影响。在FGF1处理的外植体中，顶芽和BrdU标记的细胞数量显著增加，而LY294002、Wortmannin、PD98059处理的外植体则明显减少。FGF1的作用可被LY294002、Wortmannin和PD98059所抑制。无论是否存在FGF1，LY294002、Wortmannin和PD98059处理的外植体均可通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法增加外植体间充质中的细胞凋亡。同时研究了LY294002、Wortmannin、PD98059对表面活性物质载脂蛋白C(SPC)表达的影响。LY294002和Wortmannin处理组SPC表达降低。这些发现表明，PI3K-AKT信号通路通过多种生物学过程在小鼠肺发育中起着关键作用。(C)2004爱思唯尔有限公司。保留所有权利。
We examined the roles of the PI3K-AKT signalling pathway in fetal lung development. By Western blotting, phosphorylated AKT (pAKT) was highly expressed in fetal days 12 and 14 with decreased expression thereafter. By immunohistochemistry, pAKT was expressed mainly in the respiratory epithelium of early fetal days. We examined the effects of fibroblast growth factor 1 (FGF1), PI3K inhibitors (LY294002 and wortmannin), MAPK inhibitor (PD98059) and both of FGF1 and each inhibitor on lung morphogenesis, BrdU incorporation and apoptosis. In the FGF1-treated explants, the number of terminal buds and BrdU-labelled cells increased significantly, while the LY294002-, wortmannin-, PD98059-treated explants demonstrated obvious decreases. The effects by FGF1 were inhibited by LY294002, wortmannin and PD98059. Regardless of the presence of FGF1, the LY294002-, wortmannin- and PD98059-treated explants increased apoptosis revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay in the mesenchyme of the explants. At the same time, the effect of LY294002, wortmannin, PD98059 on expression of surfactant apoprotein C (SPC) were also studied. The LY294002 and wortmannin treatments showed decreased expression of SPC. These findings suggest that the PI3K-AKT signalling pathway plays a pivotal role in mouse lung development through various biological processes. (C) 2004 Elsevier Ltd. All rights reserved.