# HEPATOPOIETINS, LIVER REGENERATION, AND CARCINOGENESIS

> **NIH NIH R01** · DUKE UNIVERSITY · 1990 · $144,581

## Abstract

Numerous past studies have shown that hepatocyte proliferation during liver
regeneration and carcinogenesis is associated with the appearance of blood
born factors that stimulate hepatocyte proliferation.  We have found that
there are only four substances in the serum that stimulate hepatocyte
proliferation.  These are Hepatopoietin A. Hepatopoietin B, Epidermal
Growth Factor (EGF), and Norepinephrine.  Fractions with Hepatopoietin A
activity treated with trypsin increase their activity and the new activity
is associated with a much smaller molecular weight.  In addition we found
that many hepatoma cell lines are secrete Hepatoma Derived Growth Factors
(HDGF's) that also stimulate hepatocyte proliferation and bind to the EGF
receptor.  The two hepatopoietins and the HDGF's are at the end stages of
their purification.  The projects aim to provide a comprehensive evaluation
of the peptide growth factors in regenerative and neoplastic liver growth.
The two hepatopoietins and the HDGF's will be completely purified and
characterized.  The interactions of these factors with other hormones will
be examined.  The existence of receptors for these growth factors will be
searched.  The expression of the genes encoding for these factors will be
also assessed in liver regeneration and neoplasia.  Interactions of these
factors will TGFb will be given particular emphasis.  New studies will also
attempt to identify the existence of other factors in the rat plasma or
serum (besides TGFb) that inhibit hepatocyte proliferation, following our
findings that the serum from control rats contain inhibitory activities for
hepatocyte proliferation that are not present in the serum from
hepatectomized rats.  Given the fact that HPTA activity increases affter
protease treatment and in view of previous studies emphasizing the presence
of protease activities on hepatocyte plasma membranes, the role of specific
hepatocyte plasma membrane proteases in the activation of HPTA during liver
regeneration will also be assessed.  Additional studies will be performed
to assess the role of EGF itself as a potential mitogen during liver
regeneration.

## Key facts

- **NIH application ID:** 3172976
- **Project number:** 5R01CA035373-07
- **Recipient organization:** DUKE UNIVERSITY
- **SAM.gov UEI:** TP7EK8DZV6N5
- **Principal Investigator:** GEORGE K MICHALOPOULOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $144,581
- **Award type:** 5
- **Project period:** 1983-07-15 → 1991-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172976

## Citation

> US National Institutes of Health, RePORTER application 3172976, HEPATOPOIETINS, LIVER REGENERATION, AND CARCINOGENESIS (5R01CA035373-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172976. Licensed CC0.

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