| Project/Area Number |
16K10037
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Ikeda Kazuyuki 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30507786)
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| Co-Investigator(Kenkyū-buntansha) |
長船 健二 京都大学, iPS細胞研究所, 教授 (80502947)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 川崎病 / ガンマグロブリン不応 / iPS細胞 / IVIG不応 / 血管内皮細胞 / RNA-sequencing解析 / GSEA解析 |
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| Outline of Final Research Achievements |
There are 10-20% of Kawasaki disease (KD) patients refractory to IVIG, and these patients sometimes suffer from coronary artery lesion. Here, we analyzed the mechanisms of IVIG resistance in KD, using a disease model of induced pluripotent stem cells (iPSCs). Dermal fibroblasts and peripheral blood mononuclear cells from IVIG-resistant and IVIG-responsive patients were successfully reprogrammed to iPSCs by the transduction of the reprogramming factors using an episomal expression vector. Endothelial cells were then differentiated from KD patient-derived iPSCs and RNA sequencing analyses were performed to compare gene expression profiles between IVIG-resistant and IVIG-responsive patients. Further studies are required to validate CXCL12 signaling as therapeutic targets for IVIG resistance in KD.
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| Academic Significance and Societal Importance of the Research Achievements |
川崎病はいまだ原因不明であり、ガンマグロブリン静注療法（IVIG）不応症例の場合には冠動脈病変を高率に合併する。そのため、IVIG不応のメカニズムを解明することは、診療上極めて重要であり、社会的意義は大変高いと考えられる。本研究結果からは、川崎病におけるIVIG不応や重症度を解明する上でCXCL12がkey moleculeであることが示唆された。今後は、今回発見したCXCL12について、in vitroとin vivoの実験系、臨床検体を用いることにより、IVIG不応川崎病における治療標的分子としての検証を行っていく予定である。
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