| Project/Area Number |
08670579
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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 | NAGOYA UNIVERSITY |
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Principal Investigator |
FUKUDA Yoshihide NAGOYA UNIVERSITY Second Department of Internal Medicine, Assistant Professor, 医学部, 講師 (40181284)
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| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Yasuo NAGOYA UNIVERSITY Second Department of Internal Medicine, Research Assistant, 医学部, 助手 (40192067)
YAMADA Masahiko NAGOYA UNIVERSITY Health Administration Center, Nagoya Institute of Technology,, 保健管理センター, 助手 (10273319)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | fibrosis / growth factor / hepatocellular carcinoma / liver / matrix metalloproteinase / MMP / tissue inhibitors of matrix metalloproteinase / TIMP / HepG2 / Huh7 |
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| Research Abstract |
Tissue inhibitors of matrix metalloproteinase (TIMPs) are specific inhibitors of matrix metalloproteinases, and three kinds of TIMPs have been identified. TIMP1 and TIMP2 have the potent growth-promoting activity for a wide range of cells. This study aimed to clarify growth-promoting activity of TIMPs in the liver using human hepatome cell lines and rat hepatocytes. HepG2 cells were found to secrete TIMPs in the serum-free media without stimulation. The concentration of TIMP2 was 7-9 times thicker than that of TIMP1. As compared with untreated FBS,removal of TIMPs from FBS showed a significant inhibition of DNA synthesis at 24 hours after incubation. Recombinant TIMPs demonstrated a dose dependent stimulatory effect. Hepatoma cell lines such as HepG2, Huh7 and PLC/PRF/5 also produced TIMP3 as well as TIMP1 and 2, which was demonstrated by estimating levels in the media and by detection of mRNA using RT-PCR.Rat hepatocytes showed significant elevations of 3H-thimidine uptake by adding bovine recombinant TIMP1. Administration of human recombinant TIMP1 resulted in no uptake of 3H-thymidine. These indicate that TIMPs function as autocrine cell growth factors in addition to inhibitors of matrix metalloproteinases. Rat liver can be applicable to the study on the precise function of TIMPs concerning liver injury by use of bovine TIMPs.
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