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The role of phosphatidic acid in platelet‐derived growth factor–induced proliferation of rat hepatic stellate cells
Author(s) -
Reeves Helen L.,
Thompson Mike G.,
Dack Clare L.,
Burt Alastair D.,
Day Christopher P.
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510310116
Subject(s) - mapk/erk pathway , platelet derived growth factor , hepatic stellate cell , growth factor , phosphatidic acid , platelet derived growth factor receptor , microbiology and biotechnology , biology , mitogen activated protein kinase , medicine , second messenger system , kinase , endocrinology , chemistry , signal transduction , biochemistry , receptor , phospholipid , membrane
Platelet‐derived growth factor (PDGF) is the most potent mitogen for hepatic stellate cells (HSCs) in vitro . The aim of this study was to investigate the role of the lipid‐derived second messenger phosphatidic acid (PA) in mediating this effect and, in particular, to determine its interaction with the extracellular signal‐regulated kinase (ERK) cascade. HSCs were isolated from rat livers. PA production was determined by lipid extraction and thin‐layer chromatography (TLC) after prelabeling cells with [ 3 H]myristate. ERK activity was measured by an in vitro kinase assay after immunoprecipitation. Mitogenic concentrations of PDGF, but not those of the relatively less potent mitogen, transforming growth factor α (TGF‐α), stimulated the sustained production of PA from HSCs. Exogenous PA stimulated HSC proliferation and a sustained increase in ERK activity, and proliferation was completely blocked by the inhibition of ERK activation with PD98059. The stimulation of ERK by PDGF was of a similar magnitude but more sustained than that caused by TGF‐α. These results suggest that the potent mitogenic effect of PDGF in HSCs may be caused, in part, by the generation of PA and subsequently by a more sustained activation of ERK than occurs with less potent mitogens that do not induce the production of this lipid second messenger.

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