Pathological mechanism of inflammatory bowel disease by inflammatory biomarker OLFM4 induction
| Project/Area Number |
15K08356
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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 |
Human pathology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Research Collaborator |
SAEGUSA Makoto
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 炎症性腸疾患 / 潰瘍性大腸炎 / クローン病 / OLFM4 / olfactomedin4 / olfactomedin 4 / b-catenin / EMT |
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| Outline of Final Research Achievements |
OLFM4 is a specific biomarker of inflammatory bowel disease(IBD). Its expression is induced biphasically. Aim of this study is clarifying the tumorigenesis mechanism of IBD by analyzing the induction of OLFM4.
OLFM4 was induced by NF-kappaB in ulcerative colitis(UC) and by AP-1(c-Jun/c-Fos) in Crohn disease(CD), independently. Its expression was correlated to the histological activity of UC and CD, respectively. Co-expression of OLFM4 and phospho-NF-kappaB/-65 was related to UC specifically, and suggested to be useful to differential diagnosis of UC and CD.
OLFM4 is a glycoprotein and binds Frizzled-7, a receptor of WNT pathway. It inhibits WNT pathway and epithelial mesenchymal transition. High expression of inflammatory foci of UC and reduction in associated tumor suggest OLFM4 might be a key molecule for the character of UC-associated tumor with high invasiveness and poor prognosis.
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| Academic Significance and Societal Importance of the Research Achievements |
潰瘍性大腸炎やクローン病などの炎症性腸疾患に特異的なバイオマーカーとして見出したOLMF4が潰瘍性大腸炎とクローン病で異なる発現誘導を受けることを明らかにし、その機構を同定した。それに基づいて、潰瘍性大腸炎とクローン病の病理組織診断上の鑑別に有用であることが明らかになった。
OLMF4はWNT系を抑制する糖蛋白質であることを明らかにし、上皮間葉連関を抑制する機能を有する。これは、炎症性腸疾患関連癌発生に関わるとともに、炎症性腸疾患関連腫瘍の浸潤能の高さに関連することが示唆される。
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Report
(5 results)
Research Products
(11 results)
