Characterization of a mouse hepatocyte growth-stimulating factor in serum of mice treated with carbon tetrachloride

The physicochemical and biological properties of a mouse hepatocyte growth-stimulating factor (mHGSF), whose amount in mouse serum increased markedly 24 h after carbon tetrachloride administration (E. Gohda et al., Life Sci. 46, 1801 (1990)), were examined. This factor was a heat-labile protein with a molecular weight of 75000. Its activity was sensitive to disulfide reduction. Maximal stimulation of deoxyribonucleic acid synthesis in cultured rat hepatocytes by this factor was greater than that by acidic fibroblast growth factor (acidic FGF) or mouse epidermal growth factor (EGF) and was comparable to maximal stimulation by human hepatocyte growth factor (hHGF), a heterodimer with a molecular weight of about 85000. The effect of mHGSF was additive to the maximal effects of acidic FGF and EGF and was synergistic with the maximal effect of insulin, but was neither additive nor synergistic with the maximal effect of hHGF. The mHGSF activity was not inhibited by a neutralizing anti-hHGF antiserum, which recognizes nonreduced hHGF but not reduced heavy and light chains of hHGF. mHGSF did not show any cross-reactivity to anti-hHGF monoclonal and/or polyclonal antibodies as measured by an enzyme-linked immunosorbent assay for hHGF. These results suggest that mHGSF is a hHGF-like factor with some structural difference from hHGF.