ET-1 cooperates with EGF to induce mitogenesis via a PTX-sensitive pathway in airway smooth muscle cells

被引:19
作者
Fujitani, Y [1 ]
Bertrand, C [1 ]
机构
[1] CIBA GEIGY LTD, DEPT RESP DIS & ALLERGY, CH-4002 BASEL, SWITZERLAND
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1997年 / 272卷 / 05期
关键词
cell proliferation; G protein; tyrosine kinase receptor; airway structural changes; endothelin-1; epidermal growth factor; pertussis toxin;
D O I
10.1152/ajpcell.1997.272.5.C1492
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have examined the mitogenic effect of endothelin-l (ET-1) alone or in combination with epidermal growth factor (EGF) in cultured airway smooth muscle cells (ASM) from guinea pig. ET-1 showed a weak mitogenic activity compared with the effect of EGF. However, when ET-1 and EGF were applied simultaneously, ET-1 synergistically enhanced the mitogenic activity of EGF. Neither inhibition of phospholipase C-beta nor depletion of protein kinase C affected this synergism. On the other hand, pertussis toxin (PTX), a G(i) protein inhibitor, abolished the synergistic effect of ET-1 on EGF-induced mitogenesis. ET-1 induced a transient mitogen-activated protein (MAP) kinase activation peaking at 5 min. In contrast, EGF induced a stronger signal that was maintained for up to 20 min. However, concomitant stimulation of ASM with ET-1 and EGF caused an enhanced MAP kinase activation compared with EGF alone. Moreover, PTX abolished the enhanced MAP kinase activation observed in this condition. These results indicate that ET-1 can interact with an EGF-induced mitogenic axis through the G(i) protein-dependent pathway, which is distinct from its direct mitogenic pathway.
引用
收藏
页码:C1492 / C1498
页数:7
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