| Project/Area Number |
17K09646
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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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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
Ikari Jun 千葉大学, 医学部附属病院, 講師 (50734604)
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| Co-Investigator(Kenkyū-buntansha) |
多田 裕司 千葉大学, 大学院医学研究院, 特任教授 (50344990)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | COPD / RAGE / 肺線維芽細胞 / 遊走能 / 組織修復 / S100A12 / p38 |
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| Outline of Final Research Achievements |
The migration of lung fibroblasts plays a pivotal role in wound repair and fibrotic processes in the lung. Although the receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of lung diseases, its role in lung fibroblast migration is unclear. The current study examined the effect of three different RAGE ligands, namely, HMGB1, S100A12, and CML, on human lung fibroblast (HFL-1) migration. HMGB1 augmented, whereas S100A12 inhibited. CML did not affect HFL-1 migration. The effect of HMGB1 was not through RAGE. However, the effect of S100A12 was mediated by RAGE. Moreover, S100A12 mediated HFL-1 migration through p38 mitogen-activated protein kinase (MAPK). In conclusion, S100A12 inhibits lung fibroblast migration via RAGE-p38 MAPK signaling. This pathway could represent a therapeutic target for pulmonary conditions characterized by abnormal tissue repair and remodeling.
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| Academic Significance and Societal Importance of the Research Achievements |
RAGEは新規バイオマーカーとして注目を集めており、その機能を明らかにする事は新たなCOPDの診断法や治療への展開が期待できる。これまで、申請者はCOPD修復メカニズムの異常に着目した研究を行ってきた。組織修復の観点から治療を探索することは既に疾患が進行したCOPD患者の治療や疾患の進展抑制に資する可能性がある。我々の知る限りRAGEのCOPD肺組織修復メカニズムへの関与を実証した研究は認めず、本研究の成果と考える。本研究により、RAGEのCOPD組織修復への関与が明らかになり、S100A12-RAGE-ｐ38経路制御による肺組織修復異常の制御を介した新規COPD治療の基盤になる成果と考える。
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