Project/Area Number |
20590723
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Shimane University |
Principal Investigator |
ISHIHARA Shunji Shimane University, 医学部, 准教授 (80263531)
|
Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
Keywords | 炎症性腸疾患 / 自然免疫 / MFG-E8 / Toll受容体 / NF-κB / Tool受容体 / MF-κB / MF-кB |
Research Abstract |
MFG-E8 deficiency is associated with acquisition of immune-mediated disorders due to the loss of tissue homeostasis. We observed altered MFG-E8 expression in inflamed colons during the acute phase of murine experimental colitis and found that treatment with recombinant MFG-E8, but not its RGD mutant counterpart, ameliorated colitis by reducing inflammation and improving disease parameters. To reveal the MFG-E8-mediated anti-inflammatory mechanism, we employed an in vitro system, which showed the downregulation of NF-κB in an LPS dependent manner. In addition, MFG-E8 altered α_vβ_3-integrin-mediated FAK phosphorylation by impeding the binding of one of its potent ligands osteopontin, which becomes activated during colitis. Our results indicated that MFG-E8 has a novel therapeutic potential for treatment of colitis. Recently, we also employed mfg-e8 KO mice for evaluating the function of MFG-E8 on intestinal inflammation. Acute experimental colitis was established by administrating of dextran sodium sulphate (DSS). We found that exacerbation of body weight loss, shorting of colon and histological inflammation in mfg-e8 KO mice during DSS-induced intestinal inflammation, as compared to those in wild mice. Additional investigations will be necessary to elucidate the role of MFG-E8 in chronic intestinal inflammation.
|