Elucidation of activation mechanism of hepatic stellate cells through mechano-transduction
| Project/Area Number |
17K15561
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General physiology
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| Research Institution | Osaka City University |
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Principal Investigator |
Urushima Hayato 大阪市立大学, 大学院医学研究科, 助教 (90755745)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | メカノトランスダクション / 肝星細胞 / 接着結合 / 肝がん細胞 / 浸透圧 / Eカドヘリン / 低浸透圧 / アポトーシス耐性 / 病態生理 |
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| Outline of Final Research Achievements |
In normal liver, hepatic stellate cells, one of the mesenchymal cells, express E-cadherin, which is mainly expressed in epithelial cells, and mechanotransduction occurs by adherens to hepatocytes via this E-cadherin, leadig to the suppression of hepatic stellate cells activation. In liver injury, the loss of this adherens junction increases the sensitivity to TGF-β produced in the surroundings, which play a role of hepatic stellate cells activation.
In cirrhotic stage, hyponatremia-induced hypo-osmotic condition induce apoptosis resisatance of hepatic stellate cells and hepatocellular carcinoma cells through mechano-receptor.
Therefore, our study revealed that mechanotransuduction regulate both the pysiology and pathology of hepatic stellate cells and hepatocellular carcinoma cells.
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| Academic Significance and Societal Importance of the Research Achievements |
肝星細胞は肝障害時に産生されたTGF-βなどの刺激因子によって活性化しコラーゲンを産生し創傷治癒に働くが、慢性肝疾患時の持続的活性化は肝線維化、さらには肝硬変を引き起こす。そのため肝星細胞の活性抑制を目的とした研究が数多く行われてきたが未だ有効な薬剤は開発されていない。今回の我々の研究は刺激因子に依らない新規の肝星細胞メカニズムを明らかにした。今回の発見は有効な肝星細胞活性化抑制剤研究の礎となる可能性がある。
また肝硬変時の低ナトリウム血症を積極的に改善することで肝発がんの重要なリスクファクターである肝硬変患者の肝がん発生リスクを減少させる可能性があると考えられる
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Report
(4 results)
Research Products
(9 results)
