Isoproterenol inhibits fibroblast growth factor-2-induced growth of renal epithelial cells

被引:17
作者
Izevbigie, EB
Gutkind, JS
Ray, PE
机构
[1] George Washington Univ, Childrens Natl Med Ctr, Childrens Res Inst, Ctr Mol Physiol, Washington, DC 20010 USA
[2] NIDR, Oral Pharyngeal Canc Branch Program, NIH, Bethesda, MD 20892 USA
关键词
basic fibroblast growth factor; isoproterenol; renal tubular epithelial cells; cAMP; mitogen-activated protein kinases; MEK; 1/2; cell proliferation;
D O I
10.1007/PL00013426
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
The signal transduction pathways modulating bFGF effects in renal tubular epithelial cells (RTEc) are not completely understood. Since the cAMP and the mitogen-activated protein kinase (MAPK) pathways can modulate the growth of RTEc, we studied whether two cAMP elevating agents, isoproterenol and 8-bromo-cAMP, would modulate basic fibroblast growth factor (bFGF) induction of MAPK activity (ERK-2) and cell proliferation in human renal proximal tubular epithelial cells (RPTEc) and Madin-Darby canine kidney cells (MDCK clone (E11)). Isoproterenol, but not bFGF, stimulated cAMP production in RPTEc and MDCKE11 cells. bFGF, isoproterenol, and 8-bromo-cAMP alone increased ERK-2 activity in both cell types. However, isoproterenol and 8-bromo-cAMP partially inhibited the bFGF induction of ERK-2 activity, but only isoproterenol inhibited the proliferation of both cell types. PD098059 (25 mu M). an inhibitor of MAPK kinase (MEK 1/2). blocked the bFGF mitogenic effects, but did not affect the 8-bromo-cAMP-induced mitogenic effects in MDCKE11 cells. These findings suggest that activation of ERK-2 is required but not sufficient for mitogenesis in RTEc. We conclude that isoproterenol inhibits the growth-promoting effects of bFGF in RTEc via MEK-dependent and -independent pathways.
引用
收藏
页码:726 / 734
页数:9
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