Mechanism of liver function improvement by cooperation of bovine hepatic sinusoidal cell lines
| Project/Area Number |
19K06431
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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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| Review Section |
Basic Section 42020:Veterinary medical science-related
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| Research Institution | National Agriculture and Food Research Organization |
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Principal Investigator |
Yoshioka Miyako 国立研究開発法人農業・食品産業技術総合研究機構, 動物衛生研究部門, 室長 (80355198)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 共培養 / 肝類洞細胞株 / 急性期蛋白質 / 炎症性サイトカイン / 牛 / 肝実質細胞 / 非実質細胞 / 肝臓 / 肝機能 / メタボローム解析 / 株化細胞 / 急性期蛋白 / LPS / 肝臓由来細胞株 / ハプトグロビン / Serum amyloid A / ウシ / 毒性評価 |
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| Outline of Research at the Start |
本研究では、申請者らが樹立したウシ肝実質細胞由来株（BH-4、BH-5）およびウシ非実質細胞の類洞内皮細胞株（B46）、筋線維芽細胞株（A26）の共培養系を用いて、薬物代謝や蛋白合成、糖および脂質代謝等の肝臓特有の機能を解析するとともに、肝実質細胞株と非実質細胞株の共培養による肝臓機能向上の機序を解明し、ウシの肝臓機能を評価可能な簡便な培養細胞による vitroの肝実質細胞培養モデルの確立を目指す。
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| Outline of Final Research Achievements |
We found that the combination of BH 4 cells (a parenchymal cell line) and B 46 cells (a non-parenchymal cell line) was optimal for enhancing mRNA expression of acute-phase proteins, Serum amyloid A and Haptoglobin, in coculture of bovine liver-derived cells. It was revealed that the enhancing effect involves contact between cells and involvement of the inflammatory cytokines IL -6 and IL -1 β secreted by B 46 cells. Metabolomic analysis of intracellular metabolites showed that multiple metabolites were increased by LPS stimulation in coculture compared with monoculture, suggesting that ATP production and nucleic acid synthesis were enhanced.
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| Academic Significance and Societal Importance of the Research Achievements |
ウシ肝臓由来の肝実質細胞株と非実質細胞株の共培養において、肝機能の向上が期待できる組み合わせが明らかとなった。この共培養系を用いることで、ウシ特有の代謝機能を保持した簡便なin vitroアッセイが可能となり、ウシの肝機能を保全する飼養方法や有害物質による肝障害の予防・治療法の開発につながる可能性がある。
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Report
(4 results)
Research Products
(2 results)
