A novel anti-integrin monoclonal antibody that attenuates mouse liver fibrosis: Mechanism of action and therapeutic application
| Project/Area Number |
26293174
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| 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)
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| 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
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Periostin promotes hepatic fibrosis in mice by modulating hepatic stellate cell activation via αv integrin interaction.2016
Author(s)
Soltani AK, McCarthy DA, McKleroy W, Azary S, Sakuma S, Ha A, Tharp K, Yokosaki Y, Hart D, Stahl A, Atabai K.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] OPN-a induces muscle inflammation by increasing recruitment and activation of pro-inflammatory macrophages.2016
Author(s)
Gina M Many, Yasuyuki Yokosaki, Kitipong Uaesoontrachoon, Peter P Nghiem, Luca Bello, Sherry Dadgar, Ying Yin, Jesse M Damsker, Heather B Cohen, Joe N Kornegay, David M Mosser, Kanneboyina Nagaraju, Eric Hoffman
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Journal Title
Experimental Physiology
Volume: 101
Issue: 10
Pages: 1285-1300
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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