2020 Fiscal Year Final Research Report
Developments of effective diagnosis and therapeutic methods for pleuroparenchymal fibroelastosis using lung transplantation model
| Project/Area Number |
18K15918
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 慢性肺線維症モデル / 上葉優位型肺線維症 / 肺移植動物モデル / 線維芽細胞 |
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| Outline of Final Research Achievements |
Pleuroparenchymal Fibroelastosis (PPFE) is a poor prognosis pulmonary fibrosis that causes rapid decrease in lung capacity.
In this study, we performed RNA-seq and protein expression analysis using a minor alloantigen mismatch lung transplantation model and PPFE cases. The results showed that although the two models were histologically similar, there were differences in mRNA and protein expression, suggesting that anti-fibrotic drugs would be a promising treatment for PPFE.
Based on these results, the therapeutic efficacy of α1-adrenoceptor antagonists in pulmonary fibrosis was examined and published in a paper. We will continue to develop novel therapies targeting the differentially expressed genes and deposition proteins obtained in this study.
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| Free Research Field |
間質性肺炎
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| Academic Significance and Societal Importance of the Research Achievements |
上葉優位型肺線維症(PPFE)の原因として特発性のほか、過敏性肺臓炎、膠原病、粉塵吸入、抗癌剤投与や放射線照射、造血幹細胞移植など多岐に及ぶため、炎症に続発する線維化か、炎症を伴わない持続する肺傷害によって生じる線維化であるのか不明であった。本研究ではPPFEと類似した線維化を呈するminor alloantigenミスマッチ肺移植モデルが、PPFEの動物モデルとして妥当か検証した。結果として、両者は発現する遺伝子やタンパクに相違があり疾患モデルとしては妥当ではなかったが、解析結果からPPFEにおいて抗線維化薬が有望であると推察される結果を得た。
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