2021 Fiscal Year Final Research Report
Could epithelial-mesenchymal transition inhibitors be a novel treatment for systemic sclerosis?
Project/Area Number |
19K08769
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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 53050:Dermatology-related
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Research Institution | University of Fukui |
Principal Investigator |
Hasegawa Minoru 福井大学, 学術研究院医学系部門, 教授 (50283130)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 強皮症 / 線維化 / 治療薬 / 動物モデル |
Outline of Final Research Achievements |
Systemic sclerosis (SSc) is a collagen disease that exhibits fibrosis in the skin and internal organs. Recently, our high-throughput in vitro screening discovered a small compound, LG283, that may disrupt the differentiation of epithelial cells into myofibroblasts (EMT). LG283 suppressed TGF-β-induced expression of extracellular matrix and α-SMA, and Smad3 phosphorylation in cultured human dermal fibroblasts. LG283 was also found to block EMT in cultured human epithelial cells. During these processes, Smad3 phosphorylation was inhibited by LG283 treatment. In the bleomycin-induced skin fibrosis model, oral LG283 efficiently protected against the development of skin fibrosis. The LG283 compound exhibits antagonistic activity on fibrosis through inhibition of TGF-β signaling pathways and thus, may be a candidate therapeutic for treatment of SSc. We also propose that the screening of EMT regulatory compounds may result in additional therapeutic approaches for tissue fibrosis.
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Free Research Field |
皮膚科学
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Academic Significance and Societal Importance of the Research Achievements |
全身性強皮症は、皮膚や内臓が線維化によって硬くなる膠原病で、厚労省の難病にも指定されている。そして、膠原病の中でも治療が難しく、新しい治療薬の開発が望まれている。本研究は多数の化合物の中から、線維化を抑制する可能性のある薬剤を独自の方法でスクリーニングし、細胞実験と動物実験で、線維化を抑制する化合物LG283を見出したものである。さらに詳細な検討を行うことにより、LG283を実際の臨床試験に発展させたい。また、本研究成果は、我々の薬剤スクリーニング法が、抗線維化薬の開発に有用な可能性があることを示すものである。
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