| Project/Area Number |
16K09898
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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 |
Collagenous pathology/Allergology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
有信 洋二郎 九州大学, 大学病院, 講師 (90467928)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | マスト細胞 / 強皮症 / 生理活性物質 / 生理活性ペプチド / 全身性強皮症 / ブレオマイシン / chymase |
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| Outline of Final Research Achievements |
In peripheral blood of patients with systemic sclerosis (SSc), endothelin 1 (ET-1) and angiotensin II (AT II) concentrations tended to be higher in SSc patients with interstitial pneumonia (IP) and those who had positive for anti-Scl-70 antibody than in healthy subjects. Serum histamine levels were elevated in SSc patients with IP or pulmonary hypertension, and correlated with pulmonary function (VC, DLCO) and IP markers (KL-6, SP-D). In addition, increased numbers of activated mast cells (MCs) were observed in skin lesions of SSc patients and the bleomycin-induced scleroderma model, and there was less severe pathology in skin lesions of MC-deficient mice or chymase-deficient mice than in the wild-type model. Taken together, a role of MCs and MC-derived chymase, through the regulation of various bioactive substances such as ET-1 and AT II, was indicated in the pathological mechanism of SSc.
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| Academic Significance and Societal Importance of the Research Achievements |
全身性強皮症は病態の解明が十分でなく有効な治療法の乏しい難治性疾患である。これまでエンドセリン-1やアンギオテンシン IIといった生理活性物質の強皮症病態形成おける役割が示されてきた。マスト細胞は強皮症皮膚病変部で増加しており、種々の生理活性物質の産生・分解にマスト細胞由来のプロテアーゼ（キマーゼなど）が関与していることより、マスト細胞がこれら生理活性物質の発現調節を通じて強皮症の病態形成に関与している可能性を本研究で検証した。その結果、強皮症病態形成におけるキマーゼや生理活性物質の役割が示唆され、マスト細胞やそのプロテアーゼをターゲットにした治療が強皮症病態に有用である可能性が示された。
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