Journal
EXPERIMENTAL CELL RESEARCH
Volume 281, Issue 1, Pages 140-147Publisher
ELSEVIER INC
DOI: 10.1006/excr.2002.5657
Keywords
actin polymerization; liver injury; cytochalasin D; signal transduction; stellate cell; tyrosine phosphorylation
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Funding
- NIAAA NIH HHS [AA11909] Funding Source: Medline
- NIDDK NIH HHS [DK57532, DK02450] Funding Source: Medline
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Although hepatic myofibroblast (HMF) migration contributes to the development of fibrosis, the mechanisms coordinating this movement are uncertain. We determined the effects of lysophosphatidic acid (LPA) and platelet-derived growth factor-BB (PDGF) on actin polymerization, FAK tyrosine phosphorylation, and migration of cultured human HMFs. LPA (0.4-100 muM) stimulated migration, FAK tyrosine phosphorylation, and stress fiber assembly with a sigmoidal dose response. PDGF (1-250 ng/ml) stimulated migration, FAK tyrosine phosphorylation, and actin polymerization with a bell-shape dose-response characterized by a maximum at 10-25 ng/ml. Concentrations of cytochalasin D, which abolished FAK tyrosine phosphorylation, also blocked LPA- and PDGF-induced migration. A dose of 1-10 ng/ml PDGF acted synergistically with LPA (10 muM) to stimulate FAK tyrosine phosphorylation and migration, whereas higher concentrations of PDGF (100-250 ng/ml) inhibited FAK tyrosine phosphorylation and migration in response to LPA (10 muM). These data indicate that PDGF and LPA coordinately govern the migration of HMFs by differentially regulating FAK and suggest a novel model in which PDGF, acting as an amplifier/attenuator of LPA-induced Signaling, facilitates HMF accumulation within injured areas of the liver. (C) 2002 Elsevier Science (USA).
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