MATSUMURA Masayuki University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
KANAI Fumihiko University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (70334399)
SHIRATORI Yasushi Okayama University, Professor, 大学院・医師学総合研究科, 教授 (70196624)
小松 裕 東京大学, 医学部・附属病院, 助手 (90301100)
|Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥5,300,000 (Direct Cost: ¥5,300,000)
Aims of this study are to clarify an intercellular interaction and signaling pathway in hepatic sinusoidal cells using molecular biology technique, and to clarify control mechanism in the sinusoidal cells. In particular, we analyzed formation mechanism of angiogenesis of endothelial cells and intracellular signal transduction mechanism in liver fibrogenesis, sinusoidal endothelial cell proliferation in liver regeneration, and endothelial angiogenesis in cancer cell metastasis. Furthermore, to clarify an important factor concerned with control and a treatment of these liver disease state.
On the stellate cell which participated in liver fibrosis, we analyzed receptor, corepressor, and coactivator of RXR/RAR in collagen production and depression, also analized signal transduction in stellate cell by various cytokine stimuration and HBV, HCV and retinol. In analysis of a signal with cell proliferation mechanism of liver sinusoidal endothelial cells in liver regeneration, we analyzed VEGF receptor, Ras-MAPK signal pathway, p38, SAPK/JNK, JAK/STAT, PI3K-Akt, and JAK/STAT.
We used reporter plasmid pHTD2 which tied a CAT gene to promoter area of TGF-b1 in elucidation of control mechanism of liver disease by gene induction and elucidation of control mechanism in hepatic fibrogenesis. Furthermore, we elucidated that HBx protein and HCV core protein activated TGF-b1 promoter in dosage dependence. At the same time we clarified signal pathway in tissue inhibitor of metalloproteinase-1, -2 (TIMP). Furthermore, we anarized coherence with RAR, RXR which were receptor in retinoic acid, corepressor, coactivator and collagen gene expression.