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PI3K-AKT pathway mediates growth and survival signals during development of fetal mouse lung
被引:44
作者:
Wang, J
Ito, T
[1
]
Udaka, N
Okudela, K
Yazawa, T
Kitamura, H
机构:
[1] Yokohama City Univ, Grad Sch Med, Dept Pathol, Yokohama, Kanagawa 232, Japan
[2] Kumamoto Univ, Grad Sch Med Sci, Dept Pathol & Expt Med, Kumamoto 8608556, Japan
[3] Natl Canc Ctr, Res Inst, Div Biol, Tokyo 104, Japan
关键词:
AKT;
morphogenesis;
proliferation;
differentiation;
apoptosis;
lung;
D O I:
10.1016/j.tice.2004.09.002
中图分类号:
R602 [外科病理学、解剖学];
R32 [人体形态学];
学科分类号:
100101 ;
摘要:
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.
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页码:25 / 35
页数:11
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