| Project/Area Number |
18591109
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Kobe University |
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Principal Investigator |
NAKAMACHI Yuji Kobe University, Hospital Clinical laboratory., Medical technologist (80379429)
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| Co-Investigator(Kenkyū-buntansha) |
KAWANO Seiji Kobe University Hospital, Clinical laboratory, instructor (20351512)
KUMAGAI Shunichi Kobe University, Graduate School of Medicine, Professor (00153346)
KOSHIBA Masahiro Hyogo college of medicine, Clinical Laboratory, Professor (70301827)
SAURA Ryuichi Kobe University, Graduate School of Medicine, Researcher (10252769)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Rheumatoid arthritis / Micro RNA |
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| Research Abstract |
Rheumatoid arthritis (RA) is a chronic disease of unknown etiology that presents a characteristic constellation of features that includes infiltrating leukocytes to synoviocytes and synoviocyte hyperplasia, resulting in pannus formation and joint destruction. The local production of cytokines and chemokines by these cells accounts for many of the pathological and clinical manifestations of RA. The molecular marker which could diagnose early RA or predict the response to currently used treatments does not exist.
Our aim was to reveal the pathogenesis of RA by analyzing the expression of micro RNA (miRNA), a novel RNA interfence factor, and to exploit the possibility of inventing a novel diagnostic method and a novel therapy.
One of the research foci was the identification of the specific miRNAs to RA fibroblast-like synoviocyte (RA-FIS). We found that five miRNAs were more strongly expressed in RA-FLS than in osteoarthritis FIS (0A-FLS), and miR-124a was the only significantly decreased miRNA in RA-FLS as compared to OA-FLS. The transfection of a precursor of miR-124a into RA-FLS suppressed their proliferation significantly and forced to stop the cell cycle at G1 phase with no significant increase of apoptosis to RA-FLS. We identified a putative consensus site for miR-124a binding in the 3UTR regions of CDK2 and MCP1 mRNA, and induction of miR-124a into RA-FLS significantly suppressed the production of CDK2 and MCP1 proteins. These results suggest that decreasing miR-124a expression in RA-FLS is deeply involved in the pathogenesis of RA.
Another research focus was to identify the RA-specific miRNAs in peripheral blood mononuclear cells (PBMC). We have been searching for RA-specific miRNA in PBMC, and preliminary data show that totally different sets of miRNAs from that of RA-FLS are anticipated.
All research expenses were spent to buy chemical reagents and disposable equipments.
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