| Project/Area Number |
21K16122
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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 | Juntendo University |
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Principal Investigator |
Kadoya Kotaro 順天堂大学, 医学部, 非常勤助教 (10849706)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Extracellular vesicles / 間葉系幹細胞 / 肺線維芽細胞 / TGF-β / micro RNA / Extracellular Vesicle / 肺線維症 |
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| Outline of Research at the Start |
本研究は、従来にない間葉系幹細胞由来Extracellular Vesicle (EV)による肺線維症の病態制御機序の解明を行い、間葉系幹細胞由来EVのタンパク質やmiRNAの新たな抗線維化標的因子の同定を行う。革新的な新規バイオ抗線維化薬剤として間葉系幹細胞由来EVの臨床応用に向けた基盤研究である。
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| Outline of Final Research Achievements |
When lung fibroblasts were subjected to TGFβ stimulation and treated with extracellular vesicle (EV) preparations derived from mesenchymal stem cells (MSCs), there was a notable inhibition of their migratory capabilities in response to fibronectin concentration gradients and a reduction in their ability to contract collagen gels. Additionally, these preparations suppressed the production of α-smooth muscle actin (αSMA) and type I collagen. Further investigations, including comprehensive miRNA analyses and miRNA mimic experiments of the MSC-derived EVs, identified a specific miRNA that exhibited anti-fibrotic effects. To explore the underlying mechanisms, the study focused on intracellular signaling pathways in the treated fibroblasts. It was demonstrated that the EV treatment suppressed fibrosis-related phosphorylation signaling and specific protein expression in lung fibroblasts, suggesting a potential therapeutic pathway for fibrotic diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、従来にない間葉系幹細胞由来Extracellular Vesicle (EV)による肺線維症の病態制御機序の解明を行い、間葉系幹細胞由来EVのタンパク質やmiRNAの新たな抗線維化標的因子の同定を行う。革新的な新規バイオ抗線維化薬剤として間葉系幹細胞由来EVの臨床応用に向けた基盤研究である。
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