The role of macrophages in NASH-related HCC and an application for therapy
| Project/Area Number |
25460973
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Akita University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肝癌 / NASH / TLR / マクロファージ / 非アルコール性脂肪性肝炎 / 腸内細菌 / Toll like receptor |
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| Outline of Final Research Achievements |
The role of Toll-like receptor (TLR) signaling has attracted much attention in the development of hepatic inflammation and hepatocellular carcinoma (HCC). We used hepatocyte-specific Pten deficient (PtenΔhep) mice, which exhibit steatohepatitis followed by liver tumor formation including HCC. We then investigated the role of macrophages. Tlr4 deficiency in the PtenΔhep mice suppressed tumor growth as well as hepatic inflammation. Gut sterilization by antibiotics reduced the portal LPS levels as well as tumor growth in the PtenΔhep mice. Tumor growth was also decreased by reconstitution of BM-derived cells to Tlr4-/- BM cells. Hepatic macrophages isolated from the PtenΔhep mice produced much more IL-6 and TNFα in response to LPS. These proinflammatory cytokines induced proliferation of HCC cells as well as oval cells, putative cancer progenitor cells. TLR4 on macrophages contributes to the development of steatohepatitis-related HCC in mice.
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Report
(4 results)
Research Products
(9 results)
