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p53 May positively regulate hepatocyte proliferation in rats
Yukiko Inoue1, Tomoaki Tomiya, Mikio Yanase
1Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Hepatology (Baltimore, Md.)
|July 27, 2002
Summary
Hepatocyte Growth Factor (HGF) stimulates p53 production, promoting rat hepatocyte proliferation. This process may involve transforming growth factor alpha (TGF-alpha) in HGF-p53 mediated liver regeneration.
Area of Science:
- Molecular Biology
- Hepatology
- Cellular Biology
Background:
- p53 acts as a tumor suppressor and transcription factor regulating cellular functions.
- Transforming growth factor alpha (TGF-alpha) promoter is a direct target of p53.
- Hepatic p53 mRNA is upregulated during liver regeneration in rats.
Purpose of the Study:
- To investigate the role of p53 in hepatocyte proliferation.
- To examine the relationship between p53, HGF, and TGF-alpha in liver regeneration.
Main Methods:
- Culturing rat hepatocytes with HGF and measuring p53 protein levels.
- Utilizing p53 antisense oligonucleotide and pifithrin-alpha to inhibit p53 activity.
- Analyzing p53, TGF-alpha levels, and DNA synthesis in cultured hepatocytes.
- Examining hepatic p53 and HGF levels in rats undergoing partial hepatectomy.
Main Results:
- HGF stimulation increased p53 protein levels in cultured hepatocytes.
- p53 antisense oligonucleotide and pifithrin-alpha suppressed p53, TGF-alpha, and DNA synthesis.
- In vivo, hepatic p53 levels peaked post-hepatectomy, correlating with HGF and TGF-alpha increases.
- Sham-operated rats showed minimal elevation in hepatic p53.
Conclusions:
- HGF stimulates p53 production, which contributes to rat hepatocyte proliferation.
- TGF-alpha may mediate the effects of HGF-p53 on hepatocyte proliferation.
- p53 plays a significant role in HGF-induced liver regeneration.