| Project/Area Number |
23791501
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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 |
General surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Research Collaborator |
HATTORI Koichi 東京大学, 医科学研究所, 特任准教授 (10360116)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 炎症性腸疾患 / マトリックスメタロプロテアーゼ / TNFα / 線維素溶解系 / 炎症性サイトカイン / 潰瘍性大腸炎 / クローン病 / YO2 / FASligand / マトリックスメタロプロテイナーゼ / MMP9 / デキストラン硫酸ナトリウム |
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| Research Abstract |
Treatment of ulcerative colitis is generally effective in relieving symptoms, but is not curative. Typically, this disease evolves with a relapsing and remitting course. Tissue remodeling by proteases like matrix metalloproteinases (MMP) have been described as a component of inflammatory bowel disease. There is mounting evidence that MMPs are the predominant proteinases expressed in the gut mucosa during active ulcerative colitis. Others and we showed that plasmin can activate several MMPs.Here, we investigated the function of MMP9 and plasminogen in a DSS (Dextran sulfate sodium) induced animal model of acute colitis. Pharmacological inhibition, an active -center-directed inhibitor or targeted gene deletion of Plg or MMP9 prevented increased morbidity of wildtype mice during DSS colitis. This was associated with a reduced inflammatory cell infiltration in colon tissues and correlated with impaired colonic cytokine level elevation. In summary, our data show that the absence of Plg and MMP9 strongly inhibits the inflammatory response in acute colitis, which is associated with alleviation of the course of the disease.
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