| Project/Area Number |
16K21668
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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 surgery
General medical chemistry
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Sasaki Kengo 国立研究開発法人国立成育医療研究センター, 臓器・運動器病態外科部, レジデント (10740871)
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| Research Collaborator |
Kasahara Mureo
Fukuda Akinari
Uchida Hajime
Yoshioka Takako
Nakazawa Atsuko
Akutsu Hidenori
Umezawa Akihiro
Machida Masakazu
Kawasaki Tomoyuki
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 胆汁酸 / オルガノイド / iPS細胞 / SLC10A2 / CYP3A4 / 腸管様構造体 / 遺伝子発現解析 / 難治性腸管吸収不全症 / 移植外科学 / 発生医学 / 疾患モデル / 難治性腸疾患 / ＰＦＩC |
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| Outline of Final Research Achievements |
Bile acids are reabsorbed in the lower part of the small intestine, transported to the liver via the portal vein, chemically conjugated, and then secreted back into the small intestine for enterohepatic circulation. Progressive familial intrahepatic cholestasis type 1 (PFIC 1) is a heterozygous mutation of the membrane protein ATP8B1 gene that causes malabsorption by secondarily decreasing the expression of bile acid transporters such as SLC10A2. In this study, we succeeded in producing small intestinal organoids from PFIC1-iPS cells, and characterized them and constructed a model for visualizing bile acid absorption. Quantitative PCR analysis revealed decreased expression of SLC10A2, a bile acid transporter, and decreased bile acid absorption compared with controls.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでPFIC1患者の肝臓における病態については数多く研究されてきているが、小腸についての研究は殆ど成されていない。小腸吸収不良の原因と関連するSLC10A2の低下と胆汁酸吸収を可視化できるシステムを構築することが出来た。これにより、SLC10A2の発現が増強する薬剤を探索・評価することが可能となりPFIC1型の創薬開発へ貢献することが出来た。
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