Mechanisms of endostatin and microRNAs in pulmonary fibrosis
| Project/Area Number |
17K09675
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Azuma Arata 日本医科大学, 医学部, 教授 (10184194)
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| Co-Investigator(Kenkyū-buntansha) |
神尾 孝一郎 日本医科大学, 医学部, 講師 (20465305)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | エンドスタチン / 筋線維芽細胞 / 上皮間葉転換 / エクソソーム / マイクロRNA / microRNA / 特発性肺線維症 |
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| Outline of Final Research Achievements |
Numerous microRNAs (miRNAs) have been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, miRNAs derived from exosomes and the relevance of such miRNAs to fibroblast-to-myofibroblast differentiation are not well understood.
Using miRNA array analysis, we profiled exosome-derived miRNA expression in sera of mice exhibiting bleomycin-induced pulmonary fibrosis. MiRNA array analysis revealed that miR-22 expression was increased on day 7 after bleomycin treatment compared with that in vehicle-treated mice. In vitro, miR-22 transfection to human lung fibroblasts suppressed TGF-β1-inducedα-SMA expression. This effect was mediated via inhibition of the ERK1/2 pathway. In vivo, administration of a miR-22 mimic on day 10 after bleomycin challenge ameliorated pulmonary fibrosis lesions accompanied by decreased α-SMA expression in the model mice. The present findings warrant further study, which could shed light on miR-22 as a novel therapeutic target in IPF.
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| Academic Significance and Societal Importance of the Research Achievements |
特発性肺線維症は肺間質の線維化と共に進行性に呼吸機能の低下を来す呼吸器難病であり。現在2つの抗線維化薬が使用可能となったが、いずれも肺活量の低下抑制が主たる作用であり、疾患の進行を完全に停止せしめるものではないのが現状である。本研究ではエクソソーム由来のマイクロRNAにより、線維芽細胞から筋線維芽細胞への分化が抑制されることが確認された。今後これらをターゲットとした特発性肺線維症の治療応用が期待される。
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Report
(4 results)
Research Products
(1 results)
