| Project/Area Number |
17K15955
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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 |
Gastroenterology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
TANAKA Shingo 札幌医科大学, 医学部, 助教 (60561024)
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| Research Collaborator |
KATO junji
MIYANISHI koji
SAKAMOTO hiroki
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| Project Period (FY) |
2017-04-01 – 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | NASH / 鉄過剰 / 酸化ストレス / IRP 1 / IRP1 / DMT1 / 8-OHdG / 鉄 |
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| Outline of Final Research Achievements |
Caco-2/TC7 cells were cultured on a porous filter in order to form monolayers having the morphology and function of small intestinal epithelial cells as in vitro experiments. It was possible to measure DMT1 mRNA expression level and IRP activity.
In vivo experiment, a steatohepatitis model mouse was prepared. It was reared in Surwit diet, iron content was added 450 mg/kg diet in iron excess group. After liver tissue was collected and fixed specimens were prepared, liver injury, fibrosis, iron deposition, degree of oxidative stress using 8-OHdG antibody, and carcinogenesis could be analyzed.
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| Academic Significance and Societal Importance of the Research Achievements |
NASHおよびこれを背景とする肝細胞癌患者が増加している.しかし成人の2-4割が罹患している脂肪肝患者からNASH患者を簡潔に鑑別する方法がなく，標準的治療法も確立していない.申請者らはこれまでに肝鉄過剰沈着がIron regulatory protein 1 (IRP1)活性の亢進を介した消化管の鉄トランスポーター発現増加により惹起されることを明らかにした.
本研究で得られた結果は，肝鉄過剰沈着を伴うNASHにおける鉄代謝異常機序の解明および新たなバイオマーカー探索について一助となるものと思われる．
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