Potential of SPACIA1 as a druggable target of rheumatoid arthritis

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Fujii Ryoji 聖マリアンナ医科大学, 医学研究科, 講師 (10333535)
• Co-Investigator(Renkei-kenkyūsha): YUDO Kazuo 聖マリアンナ医科大学, 医学研究科, 教授 (60272928) ; KOMATSU Rie 聖マリアンナ医科大学, 医学研究科, 研究技術員 (80517475)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 関節リウマチ / 滑膜 / 細胞増殖 / 炎症

Outline of Final Research Achievements

SPACIA1 is a gene associated with abnormal synovial proliferation in rheumatoid arthritis (RA). We previously showed that SPACIA1 transgenic mice exhibited early onset and rapid progression of collagen-induced arthritis (CIA). In the present study, we showed SPACIA1 could be involved in expression of CDK6 gene, a G1 phase-cell cycle factor, via mRNA stability. We also confirmed that TNF-alpha regulates CDK6 expression on transcriptional level in RA-synoviocytes. Unfortunately, even SPACIA1-deficient mice were investigated onset of CIA, therefore we focused CDK6, not SPACIA1, to assess the potential as a druggable target of RA. CDK6 knockdown by its siRNA inhibited the proliferation of RA-synoviocytes. Moreover, treatment of CDK6 inhibitor to mice almost completely prevented development of CIA.

Free Research Field

分子生物学