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Synergistic enhancement of EGF, but not HGF, stimulated hepatocyte motility by TGF‐β1 in vitro
Author(s) -
Stolz Donna Beer,
Michalopoulos George K.
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199701)170:1<57::aid-jcp7>3.0.co;2-k
Subject(s) - hepatocyte growth factor , epidermal growth factor , transforming growth factor , growth factor , motility , chemotaxis , fibronectin , hepatocyte , extracellular matrix , microbiology and biotechnology , chemistry , laminin , medicine , endocrinology , biology , cell culture , in vitro , biochemistry , receptor , genetics
The ability of TGF‐β1 (transforming growth factor‐beta 1) to suppress growth factor induced proliferation of many cell types in vitro is well documented; however, TGF‐β1 increases within a similar time frame as the hepatocyte mitogens HGF (hepatocyte growth factor), EGF (epidermal growth factor), and TGF‐α(transforming growth factor‐alpha) prior to hepatocyte proliferation during liver regeneration. This has raised the issue that TGF‐β1 may have effects on hepatocytes additional to mito‐inhibition and that these effects may be relevant to the regenerative process. To this end, we examined the effect of TGF‐β1 on both the mitogenesis and the motility of growth factor stimulated primary rat hepatocytes and the hepatoblastoma cell line HepG2 in vitro. TGF‐β1 significantly enhanced the chemotactic motility of EGF or TGF‐α, and not HGF, stimulated hepatocytes on a collagen I substratum. TGF‐β1 was not chemotactic when added alone and decreased the DNA synthesis of all hepatocyte cultures to near control levels. HepG2 cells were chemotactic toward HGF, EGF, and TGF‐β1 alone and displayed an additive chemotactic response when TGF‐β1 was added to either HGF or EGF. Additionally, HepG2 cells were refractory to the growth stimulatory effects of HGF or EGF and the growth inhibitory effects of TGF‐β1. Hepatocytes plated onto other collagen‐containing substrates (collagen IV, Matrigel, or ECL, an entactin‐collagen IV‐laminin matrix), but not on fibronectin or laminin alone, also displayed enhanced EGF stimulated motility by TGF‐β1. The data indicate that an additional, novel role for TGF‐β1 during liver tissue remodeling following PHx may include the synergistic enhancement EGF stimulated hepatocyte motility responses, and this enhancement is observed only on collagen‐containing extra‐cellular matrices. J Cell Physiol 170:57–68, 1997 © 1997 Wiley‐Liss, Inc.