| Project/Area Number |
17590633
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
FUJIYAMA Yoshihide Shiga University of Medical Science, Undergraduate School of Medicine, Professor (70111896)
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| Co-Investigator(Kenkyū-buntansha) |
ANDOH Akira Shiga University cif Medical Science, Undergraduate School of Medicine, Associate professor (90252395)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,850,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Stem cell / bone marrow transplantation / mesenchymal cells / 組織再生 / 筋繊維芽細胞 / サイトカイン / IL-22 / IL-17 / 炎症性腸疾患 |
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| Research Abstract |
Inflammatory bowel disease (IBD), ulcerative colitis (IX) and Crohn's disease (CD), is characterized by an ongoing mucosal inflammation in which a dysfunction of the host immune responses against commensal microbiota and dietary factors is involved (Riddle, 1995 ; Stenson, 1995). Intestinal inflammation has traditionally been considered as a process in which effector immune cells cause the destruction of other mucosal cells that behave as passive bystander targets. The chronic inflammatory process leads to the distruction of the epithelial barrier and formation of epithelial ulceration. This permits an easy access of luminal microbiota and dietary antiges to the cells resident in lamina propria. In this response, mesenchymal cells such as stromal fibroblsts and myofibroblasts affect the recruitment, retention and activation of immune cells, through synthesis of cytokines, chemokines, eicosanoids and extracellular matrix components. The importance of mesenchymal cells to the perpetuation of chronic inflammation has been previously appreciated in various literatures.
Resolution of inflammatory activity is associated with repair processes that facilitate tissue remodeling which restores normal intestinal architecture. Balanced repair processes are effective in restoring a normal mucosal structure, but excess fibrosis induces stricture formation which is frequently observed in CD patients. Fibrosis is typically associated with mesenchymal cell hyperplasia, tissue disorganization and fibrillar collagen deposition. The transient appearance of mesenchymal cells is a feature of normal wound healing, but the persistence of these cells is associated with excessive collagen deposition and fibrosis. Recent studies suggest that mesenchymal cells derived from bone marrow stem cells play a crucial role in the process of intestinal repair and fibrosis.
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