Differential modulation of hepatocyte growth factor-stimulated motility by transforming growth factor beta1 on rat liver epithelial cells in vitro

J Cell Physiol. 1998 Apr;175(1):30-40. doi: 10.1002/(SICI)1097-4652(199804)175:1<30::AID-JCP4>3.0.CO;2-D.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cells, Cultured
  • Chemotaxis / drug effects*
  • Collagen
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Extracellular Matrix Proteins / physiology
  • Hepatocyte Growth Factor / pharmacology*
  • Liver / cytology
  • Liver Regeneration
  • Rats
  • Transforming Growth Factor beta / pharmacology*


  • Extracellular Matrix Proteins
  • Transforming Growth Factor beta
  • Hepatocyte Growth Factor
  • Collagen