2002 Fiscal Year Final Research Report Summary
ROLE OF PPARα HUMAN HEPATIC STELLATE CELL AND HEPATOMA CELL
| Project/Area Number |
12670534
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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 | KURUME UNIVERSITY |
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Principal Investigator |
UENO Takato KURUME UNIVERSITY, RESEARCH CENTER FOR INNOVATIVE CANCER THERAPY, PROFESSOR, 先端癌治療研究, 教授 (70176618)
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| Co-Investigator(Kenkyū-buntansha) |
SAKATA Ryuichiro KURUME UNIVERSITY, MEDICAL DEPARTMENT, ASSISTANT, 医学部, 助手 (70258424)
KOGA Hironori KURUME UNIVERSITY, MEDICAL DEPARTMENT, ASSISTANT, 医学部, 助手 (90268855)
TORIMURA Takuji KURUME UNIVERSITY, MEDICAL DEPARTMENT, ASSISTANT PROFESSOR, 医学部, 講師 (60197986)
HASHIMOTO Osamu KURUME UNIVERSITY, MEDICAL DEPARTMENT, ASSISTANT, 医学部, 助手 (50289427)
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| Project Period (FY) |
2000 – 2002
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| Keywords | HEPATIC STELLATE CELL / HEPATOMA CELL / PPAR α ACTIVATOR / COX2 / IL-1 / DEDIFFERENTIATION / LIPOMICS / HEPATITIS C VIRUS |
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| Research Abstract |
The transfection activity of cyclooxgenase-2 (COX2) is suppressed because peroxisome proliferator-activalor receptor (PPAR α) activator regulates the signal of NF-kappa B. Moreover, in well-differentiated hepatocellular carcinoma (HCC), COX2 participate in dedifferentiation. This study examined whether PPARα activator would suppress the activation of human hepatic stellate cells (HSC) and the differentiation of HCC.
1) In the HSC line LI-90, and the hepatoma cell lines Huh-7, HLE, HepG2 and Hep3B, although the expressions of PPAR α and γ were detected, the expression of PPAR α was weaker than that of PPAR γ. In addition, the expression of PPAR α up-regulated by the IL-1 addition was decreased with PPAR α activator treatment.
2) After the reporter plasmid which united the luciferase gene with the COX2 promoter or the NF-kappa B responsive element was transferred into LI-90, although the activation of COX2 promoter or NF-kappa B responsive element increased by IL-1 addition, it was suppressed by PPAR α activator treatment.
This year we were scheduled to examine the dedifferentiation suppression effect of PPAR α activator in vitro using the hepatoma cell lines. However, since the establishment of an in vivo experiment system in which hepatitis C virus core protein transgenic mice can be treated with the direct fenofibrate (PPAR α activator), the following experiments are now progressing.
1) Changes of lipids in the mice are analyzed using lipomics, which makes it possible to analyze hundreds of kinds of lipid components.
2)The ultrastructural observation of liver tissues is being carried out.
3) Changes of factors related to the cell cycle of hepatic cells are examined using the Western method etc.
These findings from these studies are bang analyzed, and the relationship between hepatitis C virus and the lipid denaturation in hepatic cells is presently under examination.
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Research Products
(12 results)
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[Publications] Hironori Koga, Shotaro Sakisaka, Masaru Harada, Toshiyuki Takagi, Shinichiro Hanada, Eitaro Taniguchi, Takumi Kawaguchi, Kurumi Sasatomi, Rina Kimura, Osamu Hashimoto, Takato Ueno, Hirohisa Yano, Masamichi Kojiro, and Michio Sata: "Involvement of p21WAF1/Cip1, p27Kip1, and p18INK4c in troglitazone- induced cell-cycle arrest in human hepatoma cell lines"Hepatology. 33. 1087-1097 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Shoichiro Shishido, Hironori Koga, Masaru Harada, Hiroto Kumemura, Shinichiro Hanada, Eitaro Taniguchi, Ryukichi Kumashiro, Hiromasa Ohira, Yukio Sato, Masayoshi Namba, Takato Ueno, and Michio Sata: "Hydrogen peroxide overproduction in megamitochondria of troglitazone-treated human hepatocytes"Hepatology. 37. 136-147 (2003)
Description
「研究成果報告書概要(欧文)」より
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