2022 Fiscal Year Final Research Report
The role of vascular endothelial growth factor receptor 1 tyrosine kinase signaling in bleomycin-induced pulmonary fibrosis
Project/Area Number |
19K09291
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55040:Respiratory surgery-related
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Research Institution | Kitasato University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
江島 耕二 北里大学, 医学部, 准教授 (30327324)
天野 英樹 北里大学, 医学部, 教授 (60296481)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 肺線維症 / ブレオマイシン / VEGFR1 / TK / SDF-1 / CXCR4 |
Outline of Final Research Achievements |
Idiopathic pulmonary fibrosis is a lethal lung disease with a poor prognosis. Fibroblast proliferation amplifies extracellular matrix deposition and increases angiogenesis. VEGF is one of the most potent angiogenic factors. VEGF interacts with VEGF receptors (VEGFR1 and VEGFR2). We hypothesized that VEGFR1-TK signaling might be related to pulmonary fibrosis. C57Bl/6 wild-type (WT) mice and VEGFR1 TK knockout mice (TKKO mice) were treated with bleomycin. The expression of type I collagen, S100A4, and TGF-β was also significantly reduced in TKKO mice. TKKO mice also had significantly lower levels of SDF-1 in the lungs and plasma. Moreover, the CXCR7 and CXCR4, the receptors for SDF-1, was also suppressed in TKKO mice. Treatment with a CXCR4 antibody decreased the accumulation of VEGFR1+ cells in the lung in WT mice but not in TKKO mice.These results suggest that VEGFR1 TK signaling promotes BLM-induced pulmonary fibrosis by activating the SDF-1/CXCR4 axis in infiltrating VEGFR1+ cells.
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Free Research Field |
薬理学、呼吸薬理学、分子標的治療薬
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Academic Significance and Societal Importance of the Research Achievements |
特発性肺線維症(Idiopathic Pulmonary Fibrosis:IPF)は、特発性間質性肺炎の中で最も頻度が高く、かつ予後不良な疾患である。肺に不可逆的に進行する線維化をきたし呼吸機能が低下して致死的になる。IPFの肺組織では、Vascular Endothelial Growth Factor( VEGF)の発現増加を認め、病気の進行とそれらの発現に相関関係があると考えられている。LM誘発肺線維症モデル用いて、肺線維症の病態進行にVEGFR1-TKシグナルが関与しているか解明することにした。本研究の成果は特発性肺線維症に対し新たな治療薬の開発につながる可能性がある。
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