2018 Fiscal Year Final Research Report
Elucidation of the fibrotic mechanism of HSP47 for the treatment of intestinal fibrosis in Crohn's disease
| Project/Area Number |
16K19150
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Kyoto University |
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Principal Investigator |
HONZAWA Yusuke 京都大学, 医学研究科, 特定病院助教 (90737884)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 炎症性腸疾患 / クローン病 / heat shock protein 47 / 腸管線維化 |
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| Outline of Final Research Achievements |
We focused on heat shock protein (HSP) 47 in intestinal fibrosis in Crohn's disease, and examined its mechanism with human samples. As a result, IL-1β enhanced HSP47 expression in the human intestinal myofibroblast cell line (CCD-18Co) in addition to IL-17A. It is believed that IL-1β expression was induced via inflammasome which was multimeric protein complex. In this study, in the examination of peripheral blood mononuclear cells of CD patients with the Mediterranean fever（MEFV) gene mutation, we confirmed inflammasome activation and induction of IL-1β. This result suggested that multiple cytokine environments such as IL-1β and IL-17A in the intestinal tract of CD patients might be involved in HSP47-mediated intestinal fibrosis.
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| Free Research Field |
消化器内科
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| Academic Significance and Societal Importance of the Research Achievements |
クローン病（CD）腸管炎症では、免疫学的な観点から多くの研究が行われ、各種薬剤も登場している。その一方で、患者QOLに影響する腸管線維化の機序解明は未だ十分ではなく、治療薬も存在しない。この為、腸管線維化メカニズムの解析は将来的な治療の可能性を有している。今までのところ線維化疾患に関与するとされているHSP47はCD腸管線維化に関与し、その発現にはIL-17A以外にもIL-1βといった炎症性サイトカインも関与している可能性があり、それら制御に基づく治療の可能性も示唆された。
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