Age dependent modulation of cell growth and functions in primary culture of rat hepatocytes
| Project/Area Number |
07670593
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Tottori University |
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Principal Investigator |
MURA Tetsuo Division of Pathological Chemistry, Tottori University School of Medicine, Lecture, 医学部, 講師 (80093631)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| 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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| Keywords | primary cultured of rat hepatocytes / EGF receptor assay / inhibitory effects on hepatocytes growth by TGF-beta and IL-1beta / EGF receotor from neonatal liver / cell density dependent of cell growth / effects of dibutyryl cAMP and TPA-related intracellular signal transduction / DNA合成能に与えるTGF-βとIL-1β / 脊髄液蛋白と肝細胞増殖制御 / 加齢ラット / 初代培養肝細胞 / 肝細胞増殖能と細胞密度依存性 / EGF受容体 / 細胞周期と膜蛋白 / EGFのbinding assay / 分離肝細胞膜 / 幼若肝細胞のEGF受容体 / 加齢肝臓再生機構 / ラット初代培養肝細胞 / 細胞密度依存性増殖制御 / 微小管ネットワーク / アクチンファイバー / 細胞外マトリックス / 細胞周期調節キナーゼ / 微小管結合蛋白 |
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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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Report
(3 results)
Research Products
(5 results)
