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Metabolism of HGF-SF and its role in liver regeneration
G K Michalopoulos1, R Appasamy
1Dept. of Pathology, University of Pittsburgh, PA 15261.
Abstract:
HGF-SF is rapidly sequestered in the liver after intravenous injection. This demonstrates that liver is the major organ responsible for clearance of HGF-SF. A minor involvement of the kidney in that function was also shown. Plasma levels of HGF-SF mRNA increase by 15-17 fold rapidly after 2/3 partial hepatectomy. This increase precedes the increase of HGF-SF mRNA in liver following surgical resection. The findings strongly suggest that the observed rapid elevation in plasma HGF-SF after 2/3 partial hepatectomy is due to decrease of clearance by the liver. A mechanism is proposed whereby changes in HGF-SF levels due to removal of hepatic mass stimulate entry of hepatocytes from G0 to G1 and eventually lead to DNA synthesis.
Insights
Hepatocyte growth factor (HGF-SF) is cleared by the liver. Following liver resection, reduced HGF-SF clearance, not increased production, causes rapid plasma HGF-SF elevation, stimulating liver regeneration.
Area of Science:
- Hepatology
- Molecular Biology
- Regenerative Medicine
Background:
- Hepatocyte growth factor (HGF-SF) plays a crucial role in liver regeneration.
- The clearance mechanisms and regulation of HGF-SF levels during liver injury are not fully understood.
Purpose of the Study:
- To investigate the primary organ responsible for HGF-SF clearance.
- To elucidate the cause of rapid HGF-SF elevation following partial hepatectomy.
Main Methods:
- Intravenous injection of HGF-SF in animal models.
- Measurement of plasma and liver HGF-SF mRNA levels after 2/3 partial hepatectomy.
Main Results:
- The liver is the major organ for HGF-SF clearance, with minor kidney involvement.
- Plasma HGF-SF mRNA levels increased 15-17 fold post-hepatectomy, preceding hepatic increases.
- Rapid plasma HGF-SF elevation is attributed to decreased hepatic clearance.
Conclusions:
- Reduced liver mass after hepatectomy leads to decreased HGF-SF clearance.
- This decrease in clearance, rather than increased synthesis, drives the rapid rise in plasma HGF-SF.
- Altered HGF-SF levels likely stimulate hepatocyte proliferation, initiating DNA synthesis and regeneration.