2022 Fiscal Year Final Research Report
Discovering Novel Disease Mechanisms of Cardiac Sarcoidosis Using Transcriptome Sequencing Deribed from Human Cardiac Biopsy Sample
| Project/Area Number |
19K08554
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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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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野村 章洋 金沢大学, 融合科学系, 准教授 (30707542)
細道 一善 金沢大学, 医学系, 准教授 (50420948)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 心サルコイドーシス / RNA-seq / 心筋生検 |
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| Outline of Final Research Achievements |
Sarcoidosis cases were divided into two groups, with and without cardiac lesions, and RNA-seq was performed. In patients with cardiac lesions, activation of pathways related to BMP signaling for cardiac development and IL-5 signaling via JAK-STAT was observed. This pathway may explain the pathogenesis of cardiac sarcoidosis, but immunostaining of the BMP and JAK-STAT pathways in paraffin sections showed no significant differences.
Whole genome analysis focusing on the HLA region was performed in collaboration with Osaka University, and the HLA region significantly more common in cardiac sarcoidosis cases was identified, which is currently being submitted for publication.
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| Free Research Field |
心筋症
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| Academic Significance and Societal Importance of the Research Achievements |
本研究においては、心臓病変をもつサルコイドーシスにおいて、BMPやJAK-STAT系の経路が関与している可能性が示唆された。しかしながら本研究では心筋生検検体をすべてRNA解析に回しているため(いわゆるバルクでの解析)、解析にばらつきが大きく、更に心筋組織内の細胞種毎の遺伝子発現は評価できていない。そのため、免疫染色においては有意な変化が認められなかった可能性がある。特にサルコイドーシスなど心筋組織内での環境に個体差が大きい疾患においては、心筋細胞や免疫に関連する細胞などそれぞれの細胞腫ごとにシングルセルでの解析が望ましいことを示唆している。
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