2020 Fiscal Year Final Research Report
Constructing in vitro non-alcoholic steatohepatitis model using human cultured hepatocyte
| Project/Area Number |
18K15814
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 非アルコール性脂肪肝炎 / 肝星細胞 / TM6SF2 |
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| Outline of Final Research Achievements |
Non-alcoholic steatohepatitis, which is characterized by fat accumulation in hepatocytes, necro-inflammatory change with monocyte infiltration, and liver fibrosis due to hepatic stellate cell activation, is an increasing chronic progressive liver disease of unknown cause. In this study, the cell-to-cell interactions were verified using in vitro co-culture experiments which conditions were similar to those in liver with non-alcoholic steatohepatitis. In the co-culture of activated monocyte, cultured hepatocyte, and hepatic stellate cell, activation of hepatic stellate cells was observed in the presence of high saturated fatty acid, palmitic acid condition. Furthermore, co-culture with TM6SF2- knocked down cell lines showed activation of hepatic stellate cells and increased fatty acid synthesis in hepatocytes at the same time. This result might be considered to be one of the suitable culture systems similar to the pathophysiology of human non-alcoholic steatohepatitis.
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| Free Research Field |
慢性肝疾患
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| Academic Significance and Societal Importance of the Research Achievements |
近年、脂肪肝を特徴とする非アルコール性脂肪性肝炎が増加し、健康上の問題の一つとなっている。その背景には、正確に病態を再現した実験系が確立されていない点が挙げられる。非アルコール性脂肪性肝炎の正確な機序はまだ不明であるが、肝細胞の脂肪蓄積と膨化、腸管細菌由来因子の流入と単核球の肝内浸潤、肝星細胞活性化による膠原線維増加と肝線維化が進行し、遺伝的背景も関与する事が明らかになっている。肝細胞、単核球、肝星細胞の各培養細胞を共培養し、遺伝的なリスク因子であるTM6SF2遺伝子の条件を加味し、非アルコール性脂肪性肝炎の病態をより正確に模倣したモデルを構築することは、社会的に意義があると考えられる。
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