Differential modulation of hepatocyte growth factor-stimulated motility by transforming growth factor beta1 on rat liver epithelial cells in vitro.
We have previously shown that transforming growth factor-beta1 (TGF-beta1) enhances the epidermal growth factor- (EGF) and transforming growth factor-alpha (TGF-alpha)-stimulated motility of rat hepatocytes in an extracellular matrix (ECM)-dependent fashion (Stolz and Michalopoulos, 1997, J. Cell. Physiol., 170:57-68). We have extended this study to examine the effects of TGF-beta1 on hepatocyte growth factor (HGF) and EGF-stimulated motility of rat nonparenchymal liver epithelial cells (RLECs) in vitro and determined that chemotaxis, scattering, and monolayer wound healing by EGF was synergistically enhanced by TGF-beta1 on all ECMs examined. However, HGF-based motility, unlike EGF-stimulated motility, was modulated in an assay-dependent manner by TGF-beta1. HGF-stimulated chemotaxis was dramatically decreased by addition of TGF-beta1, but wound healing was synergistically enhanced by TGF-beta1 on all ECMs examined. HGF-based scattering was not consistently affected by TGF-beta1 on any ECM tested except on laminin, where scattering was often reduced by the concomitant addition of TGF-beta1. TGF-beta1 enhanced the motility associated with monolayer wound healing by HGF or EGF independent of DNA synthesis, because tritiated thymidine uptake was consistently reduced by 60% in the presence of TGF-beta1. The data indicate that HGF and EGF motility do not follow redundant signal-transduction pathways and that specific growth factor motility-related events, as measured by wound healing, scattering, and chemotaxis, are modulated independently by ECM and TGF-beta1.
Stolz
D B
DB
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Michalopoulos
G K
GK
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008099:Liver / Q000166:cytology; D008115:Liver Regeneration; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D003094:Collagen