Differential modulation of hepatocyte growth factor-stimulated motility by transforming growth factor β1 on rat liver epithelial cells in vitro

✍ Scribed by Donna Beer Stolz; George K. Michalopoulos

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 702 KB
• Volume: 175
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199804)175:1<30::aid-jcp4>3.0.co;2-d

✦ Synopsis

We have previously shown that transforming growth factor-b1 (TGF-b1) enhances the epidermal growth factor-(EGF) and transforming growth factor-a (TGF-a)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-b1 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-b1 on all ECMs examined. However, HGF-based motility, unlike EGF-stimulated motility, was modulated in an assay-dependent manner by TGF-b1. HGF-stimulated chemotaxis was dramatically decreased by addition of TGF-b1, but wound healing was synergistically enhanced by TGF-b1 on all ECMs examined. HGF-based scattering was not consistently affected by TGF-b1 on any ECM tested except on laminin, where scattering was often reduced by the concomitant addition of TGF-b1. TGF-b1 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-b1. 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-b1.