Project: Research project

Project Details


The goal of this proposal is to investigate the role of a putative
liver-specific growth factor, hepatic stimulator substance (HSS),
in liver regeneration and compare its effects with other mitogens,
e.g., insulin like growth factors or transforming growth factors.
Specific experiments will be performed as follows: 1) In vitro
cell cycle specific effects of HSS and other mitogens in defined
culture conditions will be characterized with HSS responsive,
putative liver stem cells of epithelial origin (FNRL). Cell cycle
curves will be generated by (3H)-thymidine incorporation and cell
cycle subpopulations will be analyzed by flow cytometry. To
determine which cell subpopulation is specifically responsive to
HSS, GO/GI, S, or G2/M phase cells will be purified by centrifugal
elutriation and exposed to mitogens. Simultaneous analysis will
be performed of cell cycle related gene expression (e.g., c-fos,
c-myc, c-Ha-ras). In vivo experiments in rats will determine
whether HSS induces similar changes in gene expression. 2) To
study whether HSS induces early events in membrane signal
transduction, as opposed to later events such as nuclear gene
activation, Na+ and Ca++ ion fluxes will be determined by NMR
spectroscopy and tyrosine kinase activation will be determined by
a peptide phosphorylation assay. 3) Whether HSS enhances in vivo
proliferation of hepatocytes, or hepatocyte precursor cells with
or without an introduced albumin gene, will be determined by
transplanting HSS pretreated cells, or by administering HSS
following transplantation into normal and analbuminemic rats.
Effective start/end date7/1/896/30/94


  • Medicine(all)