Grant-in-Aid for Co-operative Research (A)
|Allocation Type||Single-year Grants|
|Research Institution||GIFU UNIVERSITY|
MUTO Yasutoshi GIFU UNIVERSITY SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (20010069)
OKITA Kiwamu YAMAGUCHI UNIVERSITY SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (70107738)
KAMATA Takenobu OSAKA UNIVERSITY MEDICAL SCHOOL,PROFESSOR, 医学部, 教授 (80028399)
WAKE Kenjiro TOKYO MEDICAL AND DENTAL UNIVERSITY,SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (00046963)
KUROKAWA Kiyoshi FACULTY OF MEDICINE,UNIVERSITY OF TOKYO,PROFESSOR, 医学部, 教授 (30167390)
ASAHIKAWA Michimito MEDICAL COLLEGE,PROFESSOR, 教授 (60000981)
|Project Period (FY)
1992 – 1994
Completed(Fiscal Year 1994)
|Budget Amount *help
¥12,000,000 (Direct Cost : ¥12,000,000)
Fiscal Year 1994 : ¥5,000,000 (Direct Cost : ¥5,000,000)
Fiscal Year 1993 : ¥7,000,000 (Direct Cost : ¥7,000,000)
|Keywords||CYTOTOXIC T CELL / NATURAL KILLER CELL / EXTRATHYMIC T CELL / EXTRACELLULAR MATRIX / TRANSFORMING GROWTH FACTOR-BETA / HEPATIC MICROCIRCULATION / APOPTOSIS / AUTONOMIC NEURON GOVERNING BOTH THE LIVER AND PANCREAS / HGF / 肝細胞膜 / 接着分子 / IFN-γ / 肝細胞増殖仰制因子 / 肝細胞多層集合体 / 伊東細胞|
1.Mechanisms of liver cell death
(1)HLA class I B44 restricted cytotoxic T cell population agaist HCV core antigen was identified in the peripheral blood of patients with type C chronic hepatitis. (2)Neither genomic DNA fragmentation, Fas ligand nor phenotypic experssion of bc1-2 which inhibits Fas system was not observed in biopsied liver specimen obtained from type C chronic hepatitis patients. (3)Activated Kupffer cells were further promoted to scavange apoptotic liver cells.
(1)Interferon-gamma induced apoptosis in liver cells while hepatocyte growth factor(HGF)cancelled such effect of interferon-gamma. (2)Tumor necrosis factor-alpha induced hepatic sinusoidal contraction and subsequent liver ischemia.
Increased expression of c-met, a potent HGF receptor, preceded the surge of DNA synthesis in the process of liver cell reganeration.
4.Signal transduction of HGF
Both following liver cell damage and partial hepatectomy, signal transduction of HGF to stimulat
e liver regeneration required activation of protein phosphatases.
5.Inhibitory factors against liver regeneration
(1)Transforming growth factor(TGF)-beta may impair liver regeneration when being over-expressed in the liver or appearing in advance of HGF expression. In addition, TGF-beta 1 expression was observed in the area of psuedo choledochal regeneration in the liver of patients with fulminant hepatitis. (2)Presence of a possible novel factor which inhibits hepatocyte growth was suggested in the plasma of fulminant hepatitis patients.
Liver cell adherence and ligand-receptor binding of HGF depended on the ECM where the cells sit on, including molecular species of proteoglycans. Thus, ECM regulated liver cell regeneration.
7.Hepatic innervation and liver regeneration
Liver regeneration may be regulated in a manner of multiple organ relationship, which network includes automonic neurons governing both the liver and the pancreas.
Not only Ito cells but also Kupffer cells regulated the sinusoidal blood flow,
9.Liver regeneration and immune system
It was suggested that natural killer cells and extrathymic T cells may damage the regenerating liver cells Less