| Project/Area Number |
17K09396
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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 |
Gastroenterology
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
工藤 正俊 近畿大学, 医学部, 教授 (10298953)
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| Project Period (FY) |
2017-04-01 – 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 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 炎症性腸疾患 / ストレス応答 / 発癌 / HSP27 / 癌 |
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| Outline of Final Research Achievements |
Stress responses to chronic inflammation promote the development of colorectal and liver cancer. Using knock-out mice, we clarified the role of Heat shock protein (HSP) 27 for tumorigenesis in the liver and colon. HSP27 is involved in the pathogenesis of liver and colorectal cancer. Gankyrin (GK) is an oncoprotein which regulates inflammatory responses and its inhibition is considered as a possible anti-inflammatory therapy for inflammatory bowel disease (IBD). Unexpectedly, GK-deficiency in the upper small bowel augmented inflammatory activity. Examination of human samples have confirmed that the reduction of GK expression in the small bowel is associated with colonic involvement in human Crohn’s disease. Through the sequencing of bacterial 16S rRNA gene amplicons, bacteria potentially deleterious to intestinal homeostasis were identified. These results provide important insights into the pathogenesis of IBD.
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| Academic Significance and Societal Importance of the Research Achievements |
大腸上皮細胞および肝実質細胞でのHSP27の機能を解明し、新しい治療およびバイオマーカーの標的分子としての有用性が明らかとなった。大腸粘膜におけるHSP27の発現量は発癌リスクの予測に有用である。またWhole transcriptome解析により、炎症性腸疾患関連大腸癌の再発と相関する遺伝子セットを同定した。本研究の成果は大腸癌サーベイランスの効率化につながる。次世代シークエンサーを用いた解析により、TNF阻害薬の治療効果を予測する遺伝子セットおよび腸内細菌叢を同定した。炎症性疾患および癌領域における個別医療の実現に向けて、更なるデータの蓄積を行っていく。
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