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Growth factor signal transduction immediately after two-thirds partial hepatectomy in the rat
D B Stolz1, W M Mars, B E Petersen
1Department of Cell Biology, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Cancer Research
|August 27, 1999
Summary
Hepatocyte growth factor (HGF) signaling is initiated within one minute after partial hepatectomy (PHx), driving liver regeneration. This study investigated early growth factor receptor activation following liver resection.
Area of Science:
- Hepatology
- Molecular Biology
- Cell Signaling
Background:
- Liver regeneration after partial hepatectomy (PHx) is a model for growth factor signaling.
- Aberrant growth factor signaling is implicated in liver cancer.
Purpose of the Study:
- Investigate early growth factor signals initiating hepatocyte proliferation after PHx.
- Evaluate tyrosine phosphorylation of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) receptors post-PHx.
Main Methods:
- Compared tyrosine phosphorylation of EGF and HGF receptors in rat livers after PHx versus sham operation.
- Assessed phosphorylation of downstream signaling molecules like paxillin and Rho A.
- Detected urokinase-type plasminogen activator (u-PA) and its receptor interactions.
Main Results:
- EGF receptor phosphorylation increased by 60 min post-PHx.
- HGF receptor (c-Met) showed biphasic phosphorylation increases at 1-5 min and 60 min post-PHx.
- u-PA and u-PA receptor co-immunoprecipitated with c-Met 1 min post-PHx.
- Paxillin phosphorylation increased rapidly post-PHx, while Rho A activation occurred later.
Conclusions:
- HGF-related signal transduction is initiated within one minute after PHx.
- Early signaling events involving HGF receptor activation contribute to liver regeneration.