A treatment strategy for pulmonary fibrosis targeting fibroblast adaptation to tissue acidosis
| Project/Area Number |
18K08157
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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 53030:Respiratory medicine-related
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肺線維症 / 間質性肺炎 / 線維芽細胞 / アシドーシス / 炭酸脱水素酵素 IX / 炭酸脱水素酵素 / ブレオマイシン / 特発性肺線維症 / Carbonic anhydrase IX / アスドーシス / 線維細胞 / 酸性環境 |
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| Outline of Final Research Achievements |
Recent studies have shown that fibrotic tissue particularly in the lung is acidic because of enhancement of glycolysis due to tissue hypoxia. This study was aimed to determine whether carbonic anhydrase IX, which regulates extracellular and intracellular pH, plays an important role in the survival and activation of fibroblasts in pulmonary fibrosis. We found that treatment of normal human fibroblasts with transforming growth factor β induced extracellular acidification by stimulating glycolysis. We also found that treatment of bleomycin-exposed mice with U-104, a selective inhibitor of carbonic anhydrase IX, improved lung tissue accumulation of collagen and lung tissue stiffness. These results suggest that CA IX is a therapeutic target for pulmonary fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
特発性肺線維症の治療成績は十分ではなく、新規治療薬の開発が望まれている。近年、線維化肺組織では解糖系が亢進して酸性化していることが報告されているが、本研究では肺線維芽細胞が線維化組織で生存、活性化するためには細胞内外のpHを調節するCarbonic anhydrase IX (CA IX)が重要な役割を果たしていることが示された。CA IXは肺線維症の新しい治療標的になると考えられた。
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Report
(4 results)
Research Products
(1 results)
