| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Many metabolic functions besides proliferation are regulated by cell density and that there is a reciprocal relation between cell growth and expression of hepatocyte-specific functions. On the other hand, old rat hepatocytes in primary culture are well known not to respond normally to EGF.Therefore, we examined whether any reciprocal related between cell growth and expression of hepatpcytes-specific functions could be demonstrated in old rat hepatocytes by change in cell density or addition of plasma membrane protein from adult and old rat liver.
The following results were obtained : (1) interleukin 1beta strongly inhibited DNA synthesis of adult and neonatal rat hepatocytes in primary culture induced by EGF plus insulin. Their inhibitory effects on hepatocyte growth were influenced reciprocally by cell density ; the inhibitory effects by TGF-beta was strong at low cell density, but weak at high cell density, whereas growth inhibition by IL-1beta was higher at high cell density. (2) Futhermore, effects of dibutyryl cyclic AMP and 12-O- tetradec anoylphorbol-13-acetate (TPA) -related intracellular signal transduction by TGF-beta and IL-1beta on growth of hepatocytes are also reciprocally modulated by cell density. Both TPA and db-cAMP alone had no effecton DNA synthesis of hepatocytes. But, TPA enhanced markedly DNA synthesis stimulated by EGF plus insulin at high cell density, and showed no effect at low cell density. ON the other hand, db-cAMP showed dual effect on growth of hepatocytes : at low concentration, at low cell density and exposure at erly stage of G1 phase enhanced DNA synthesis but at high cell density and at late stage of G1 phase, inhibited DNA synthesis. These results showed that signal transduction pathway involved in growth inhibition and stimulation in adult rat hepatocytes in primary culture was controled by cell densuty.
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