| Project/Area Number |
25461604
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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) |
HAMAOKA Kenji 京都府立医科大学, 大学院医学研究科, 教授 (60189602)
OSAFUNE Kenji 京都大学, iPS細胞研究所, 教授 (80502947)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 川崎病 / iPS細胞 / IVIG不応 / ガンマグロブリン不応 / 血管内皮細胞 / マイクロアレイ法 / 新規疾患モデル / ガンマグロブリン療法(IVIG) / IVIG不応川崎病 / マイクロアレイ |
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| Outline of Final Research Achievements |
Objective: This study clarifies the mechanisms of IVIG resistance in Kawasaki disease (KD) using an iPSC disease model.
Methods and Results:Dermal fibroblasts or PBMNCs from two IVIG-resistant and two IVIG-responsive KD patients were reprogrammed by the episomal vector-mediated transduction of reprogramming factors. KD patient-derived iPSCs were differentiated into ECs (iPSC-ECs). The gene expression profiles of iPSC-ECs generated from IVIG-resistant and IVIG-responsive KD patients were compared by RNA-sequencing analyses. We found that the expression of chemokine X was significantly up-regulated in iPSC-ECs from IVIG-resistant KD patients. Additionally, GSEA revealed that gene sets involved in IL-6 signaling were also up-regulated.
Conclusions:Our mechanistic analyses suggest that chemokine X, which plays a role in leukocyte transmigration, is a candidate key molecule for IVIG resistance. They also indicate that up-regulation of IL-6 related genes may be involved in this pathogenesis.
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