| Project/Area Number |
20K09903
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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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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
寺尾 豊 新潟大学, 医歯学系, 教授 (50397717)
前川 知樹 新潟大学, 医歯学系, 研究教授 (50625168)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 誤嚥性肺炎 / 肺炎球菌 / Pneumoniae-omics解析 / プロテアーゼ / マクロライド / Pneumonia-omics解析 / 肺炎 / プロテオーム解析 / マクロライド系抗菌薬 |
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| Outline of Research at the Start |
誤嚥性肺炎等の肺炎は，薬剤耐性菌の増加と高齢社会の到来で増加・難治化・重症化している．本申請研究では，新たなタンパク質解析技術を採り入れ，肺炎に罹患した際に免疫細胞を傷害する分子群を，細菌と免疫の両側面から網羅的に同定し，肺炎重症化機序を統合的に解明する．さらに，得られる結果から，抗菌薬に代わる分子標的薬の開発研究を，創薬実績のある連携研究チームと協同して行う．
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| Outline of Final Research Achievements |
The aim of this research project is to comprehensively elucidate the mechanisms underlying the progression of severe pneumonia. To achieve this, bronchoalveolar lavage fluid was collected from mice intratracheally infected with Streptococcus pneumoniae, as well as from uninfected mice, and proteome analyses were performed using iTRAQ. As a result, we identified multiple pneumococcal proteins and over 1,000 different host proteins. Among these pneumococcal proteins, we found that TpiA binds to plasminogen and promotes its activation, leading to the degradation of the extracellular matrix. Among host proteins, we reported that MHC class I and epidermal growth factor receptor were degraded by neutrophil elastase, which may be associated with the exacerbation of pneumococcal pneumonia.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，肺炎の重症化に関わる分子機構を解明し，肺炎（Pneumonia）をヒトと細菌の両側面から統合的に検索する”Pneumonia-omics”研究領域を開拓した．本研究成果を基盤とし，薬剤耐性の有無に関わらない新規の肺炎制御法を開発する予定である．肺炎球菌感染症をを軽症化・治療補助する薬剤開発の提案ができれば，わが国において5,000億円以上の医療費が削減されると推計される．
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