2024 Fiscal Year Final Research Report
Investigation of the interstitial microenvironment in potentiating the anti-fibrotic effects of vitamin E analogues in hepatic fibrogenesis
| Project/Area Number |
21K11683
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 59040:Nutrition science and health science-related
|
|---|
| Research Institution | Seitoku University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
藤原 葉子 お茶の水女子大学, 名誉教授 (50293105)
日下部 守昭 東京大学, 大学院農学生命科学研究科(農学部), 特任教授 (60153277)
|
|---|
| Project Period (FY) |
2021-04-01 – 2025-03-31
|
| Keywords | 肝線維化 / ビタミンE / 間質 / 細胞・組織 |
|---|
| Outline of Final Research Achievements |
Administration of vitamin E is the sole medication for nonalcoholic steatohepatitis (NASH), but its efficacy in human clinical studies has been inconsistent. One reason for this is that the efficacy of vitamin E analogues is expected to be influenced by the interstitial environment, which differs depending on the stage of the disease. In this study, we focused on tenascin-C (TNC), an extracellular matrix that determines the interstitial environment during tissue injury, and examined its relationship to the therapeutic efficacy of vitamin E analogues. In diet-induced NASH model mice, vitamin E analogues, especially tocotrienol (T3), significantly reduced the expression of hepatic fibrosis-related genes during the early onset and healing process. It was also suggested that the effect of T3 during the healing process was influenced by TNC expression and localization.
|
| Free Research Field |
機能形態学 栄養化学
|
| Academic Significance and Societal Importance of the Research Achievements |
NASHは重篤化すると肝硬変や肝癌へと進展する生活習慣関連疾患で、近い将来、肝癌の主因になると考えられている。NASHに特化した治療薬は開発途上であり、ビタミンE投与は、今もなお唯一の薬剤療法である。しかしビタミンE投与は治療効果への期待と長期投与に伴う副作用への懸念のバランスから、絶対的選択肢にはなっていない。本研究成果は、ビタミンE、特にT3は、NASH発症初期および初期病態からの緩徐な回復期において線維化抑制効果を発揮すること、間質環境によってその効果が失われることを示している。ビタミンEの短期投与に適した病期の判断や、同族体を含めた新規配合治療製剤開発の一助となることが期待される。
|
