The study for suppression of obliterative bronchiolitis by inhibiting autotaxin activity
| Project/Area Number |
25670604
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
YUKIKO Tando 東北大学, 医学(系)研究科(研究院), 非常勤講師 (70596212)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Takashi 東北大学, 加齢医学研究所, 教授 (10195901)
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| Co-Investigator(Renkei-kenkyūsha) |
AOKI Junken 東北大学, 薬学研究科, 教授 (20250219)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 肺移植 / LPA / モデルマウス / 閉塞性細気管支炎 / 移植 / 免疫学 / オートタキシン |
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| Outline of Final Research Achievements |
Obliterative bronchiolitis (OB), a fibroproliferative disorder of the small airways, is the main manifestation of chronic lung allograft rejection. Because of poor understanding of the mechanism, there is currently no treatment of this disease. The aim of this study was to repress OB by the administration of a autotaxin (ATX) inhibitor or lysophosphatidic acid (LPA) receptors (LPARs) antagonist.
The administration of Ki16198 attenuated airway epithelial cell loss in the heterotopic tracheal transplant allograft model. The number of apoptotic epithelial cells was decreased in the allografts treated with Ki16198. In addition, LPA inhibited the attachment of BEAS-2B to the ECM, which was restored by the presence of Ki16425. Accordingly, LPA signaling is involved in the loss of airway epithelial cells through the inhibition of cell adhesion to the ECM in an alloimmune-environment. This finding suggests LPA as a novel therapeutic candidate target in human OB after lung transplantation.
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Report
(3 results)
Research Products
(1 results)
