Project/Area Number |
16K19472
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Respiratory organ internal medicine
|
Research Institution | University of Occupational and Environmental Health, Japan |
Principal Investigator |
Keishi Oda 産業医科大学, 医学部, 助教 (00625527)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 特発性肺線維症 / 細菌叢解析 / miRNA / エピジェネティクス制御 |
Outline of Final Research Achievements |
The 16S rRNA was purified from BALF obtained in patients with IPF and analyzed using next-generation sequencing techniques to characterize the bacterial communities. In addition, we investigated to identify miRNAs, which changed the expression levels during acute exacerbation (AE) of IPF, and the associated genes regulated by the miRNAs through the comprehensive analysis of paired serum miRNA expressions at stable and AE periods. The most prevalent lung phyla were Firmicutes and Proteobacteria. We extensively analyzed serum miRNA expression levels and identified several miRNAs, which expression levels were significantly changed during the AE period compared to the stable period. Among them, we respectively introduced miR-122-5p and miR-151b, which we could confirm the changes in expression levels using real-time PCR, into A549 cells. Intracellular overexpression or suppression of these miRNAs revealed that they appeared to regulate gene expressions associated with extracellular matrix.
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Academic Significance and Societal Importance of the Research Achievements |
難病指定を受けている特発性肺線維症の病態は未だ不明な点が多い。我々は今回、肺内細菌叢とエピジェネティクス解析を行い、さらに急性増悪時に増減するmiRNAの特定および機能解析を行うことでバイオマーカーおよび治療ターゲットになる可能性について検討した。本研究成果によって特発性肺線維症の病態全てを紐解くことは困難であるが,本疾患に関する理解を深めるために重要な役割を果たしたと考える。
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