2022 Fiscal Year Final Research Report
possibilityof new therapeutic agent for systemic screlosis by anti-CTGF antibody
Project/Area Number |
18K08415
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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 54020:Connective tissue disease and allergy-related
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Research Institution | Juntendo University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2023-03-31
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Keywords | 強皮症 / 坑CTGF抗体 / 坑線維化 / 間質性肺炎 / 皮膚硬化 / 炎症性サイトカイン |
Outline of Final Research Achievements |
Systemic sclerosis (SSc) is known to be refractory disease due to fibrosis of the skin and internal organs. Although connective tissue growth factor (CTGF) has been well-documented in SSc fibrosis, CTGF has not been fully investigated. We studied the effects of Anti-CTGF antibody in SSc mice model. We examined pulmonary fibrosis and skin fibrosis in the mice model. Dermal sclerosis, pulmonary fibrosis and cytokine production were assessed. As for skin and pulmonary fibrosis in the topoisomeraseⅠ mice model, there were no statistically significant difference in the treatment with anti-CTGF antibody, but it had tendency to mitigate both fibrosis. In terms of fibrotic cytokine, SPP1 and α smooth muscle actin (ACTA2) had tendency to be reduced by treatment with anti-CTGF antibody. Anti-CTGF antibody may have anti-fibrotic effects in mice models of systemic sclerosis. Further researches are required to evaluate it.
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Free Research Field |
自己免疫疾患
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Academic Significance and Societal Importance of the Research Achievements |
CTGFはCCN familyに属する成長因子であり、皮膚、心臓、肺、肝臓や腎臓を含む多臓器の線維化のhallmarkであり、CTGFを標的とした抗線維化薬はSScの主要病変の皮膚硬化を改善するのみならず、間質性肺炎、肺高血圧症、強皮症腎ならびに腸管の線維化等の重篤な内臓合併症を抗CTGF抗体で同時に改善することが我々の研究結果から予測されることが研究成果の学術的意義である。またSScの根源的病因である線維化を抗CTGF抗体投与にて抑制することにより、SScの生命予後の改善を期待できることが社会的意義である。
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