| Project/Area Number |
16K08472
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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 |
General anatomy (including histology/embryology)
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| Research Institution | Osaka City University |
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Principal Investigator |
Ikeda Kazuo 大阪市立大学, 大学院医学研究科, 教授 (80275247)
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| Co-Investigator(Kenkyū-buntansha) |
松原 勤 大阪市立大学, 大学院医学研究科, 准教授 (20628698)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肝星細胞 / 肝線維化 / ヒストンバリアント / 線維化 |
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| Outline of Final Research Achievements |
Hepatic stellate cells work as sinusoidal pericytes and store vitamin A-associated lipid droplets. In liver injury, hepatic stellate cells proliferate and produce a large amount of extracellular matrixes. Stellate cells activation is an important event in pathology of liver diseases because it is believed to play a role in the development of fibrosis. In this study, we assessed the roles of histone variants H3.3 and H2A.Z in the activation of hepatic stellate cells. Chip analysis revealed that histone variants were accumulated in the regions of the genes, such as alpha-SMA and collage1A2, in activated stellate cells. We also performed genome-wide chip-sequence in hepatic stellate cells. We have been still investigating the specific regions related to stellate cells activation.
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| Academic Significance and Societal Importance of the Research Achievements |
C型慢性肝炎に対する抗ウイルス療法は劇的な進歩を遂げているが、Ｂ型慢性肝炎や脂肪肝の一部が慢性肝炎化した脂肪性肝炎、NASHの画期的な治療薬はなく、これら慢性肝炎に引き続き肝硬変、肝癌を生じることがわかってきており、大きな社会問題となっている。エピジェネティクス制御と線維化に関連する遺伝子やマイクロRNAの発現制御の関連を明らかにすることができれば、未だ特出すべき治療法が開発されていない難治性疾患である肝硬変やその他の臓器線維症の創薬開発の可能性も期待される。
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