Regulation of rheumatoid synovial fibroblasts focusing on layilin-dependent epithelial-mesenchymal transition-like changes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08896
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Kato Tomohiro 聖マリアンナ医科大学, 医学部, 教授 (80233807)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Layilin / 滑膜細胞

Outline of Final Research Achievements

We here demonstrated that layilin promotes mitochondrial fission by cyclin-dependent kinase 1 and dynamin-related protein 1 activation in HEK293T cells. As the shift from tubular to fragmented mitochondria has been reported to correlate with the enhancement of tumor cell migration and invasion, this data gives supporting evidence that layilin enhances invasive abilities through EMT-like changes. In addition, we found that cell proliferation slowed down in layilin-knockdown (KD) cells. These data suggest that layilin is deeply involved in enhancement of cell invasion and proliferation resulting from EMT-like changes.

Free Research Field

自己免疫疾患及びプロテオミクス

Academic Significance and Societal Importance of the Research Achievements

本研究によりLayilin がEMTおよびその結果起こる細胞の増殖能・浸潤能の獲得に深く関わることが強く示唆された。より長期的な目標は、滑膜細胞の EMT 様変化の抑制、それによる異常増殖抑制・骨浸潤抑制により、 RA を治療する方法を実現することである。著効はするが高価でかつ易感染性などの副作用のある現在の生物学的製剤やJAK阻害薬とは全く機序の異なる治療法を可能とすることであり、実用上の極めて大きな意義である。