| Project/Area Number |
15H04810
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
真鍋 良幸 大阪大学, 理学研究科, 助教 (00632093)
三善 英知 大阪大学, 医学系研究科, 教授 (20322183)
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| Research Collaborator |
Ono Masafumi
Sumida Yoshio
Hyogo Hideyuki
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | NAFLD/NASH / バイオマーカー / フコシル化ハプトグロビン / Mac-2 binding protein / Fut8 / NASH/NAFLD / NASH / Mac-2bp / NAFLD / 肝臓学 / 糖鎖 / fucosylation |
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| Outline of Final Research Achievements |
We found that liver fucosylation increased during the progression of nonalcoholic fatty liver disease (NAFLD). Using biopsy-proven 510 NAFLD patients and 2122 health checkpup subjects, we developed two glyco-biomarkers, fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac-2bp). These glyco-biomarkers were superior than other conventional biomarkers, and well-diagnosed NAFLD disease severity. We found that Fuc-Hpt is a useful for the prediction of ballooning hepatocyte presence, and Mac-2bp is useful for the diagnosis of liver fibrosis progression in NAFLD patients. Combination of these biomarkers can be used as a superior NAFLD biomarker.
Among fucosylation, core-fucosylation specially increased in NAFLD liver. We previously found core-fucose specific lectin, PhoSL, from Japanese mushroom. PhoSL administration improved NAFLD development in mouse NAFLD model. This result suggested the utility of PhoSL lectin as a “glyco-therapy” for NAFLD.
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| Academic Significance and Societal Importance of the Research Achievements |
NAFLD診断はこれまで確立した方法が肝生検による組織診断しかなかった。治療効果判定のために頻回に肝生検を行うことは困難であるため、非侵襲的に病態進展を評価する方法の開発が喫緊の課題となっている。本研究によって糖鎖バイオマーカーにより、血液を用いてNAFLD病態進展を評価することが可能となった。またマウスを用いた基礎的研究によってPhoSLというキノコから抽出したタンパク質がNAFLD病態進展を抑制することがわかった。PhoSLはコアフコースという糖鎖に結合するタンパク質である。本研究の成果は糖鎖を標的とした新しいヒトNAFLD治療法の開発につながるものと期待される。
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