Journal
PEDIATRIC NEPHROLOGY
Volume 14, Issue 8-9, Pages 726-734Publisher
SPRINGER-VERLAG
DOI: 10.1007/PL00013426
Keywords
basic fibroblast growth factor; isoproterenol; renal tubular epithelial cells; cAMP; mitogen-activated protein kinases; MEK 1/2; cell proliferation
Categories
Funding
- NHLBI NIH HHS [R0-1HL 55605] Funding Source: Medline
- NIDDK NIH HHS [DK49419-S1, R0-1DK 4919] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available