Project/Area Number |
26293174
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Hiroshima University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
茶山 一彰 広島大学, 医歯薬保健学研究院(医), 教授 (00211376)
正木 崇生 広島大学, 大学病院, 教授 (30397913)
仙谷 和弘 広島大学, 医歯薬保健学研究院(医), 講師 (30508164)
|
Research Collaborator |
TSUJINO KAZUYUKI カリフォルニア大学, サンフランシスコ校・肺バイオロジーセンター, 博士研究員
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
|
Keywords | fibrosis / antibody drug / integrin / myofibroblast / stellate cell / インテグリン / 肝線維症 / ノックアウトマウス / 抗体医薬 / TGF-β / 肺線維症 / 線維化 / インテグリンα8β1 / α-smooth muscle actin / 肝硬変 / 腎線維症 / 筋線維芽細胞 / 阻害抗体 / 腎硬化症 |
Outline of Final Research Achievements |
The first integrin α8β1 blocking mAb (Patent 2011-537260) we have generated showed drastic effects on mouse hepatic fibrosis (Grant-in-aid for challenging exploratory research). We have analyzed α8β1 and demonstrated its weak TGF-β activation, expression on activated stellate cells, and induction of myofibroblastic differentiation. In the present study, to develop the mAb into a medical drug, we investigated anti-fibrotic effects on pulmonary and kidney fibrosis of the mAb, α8 expression on human fibrotic livers, anti-fibrotic effect in fibroblast specific α8 KO mice and epitope mapping of the mAb, which confirmed a potency of the mAb as a medical drug.
|