2003 Fiscal Year Final Research Report Summary
Molecular cloning and functional analysis of genes associated with mucosal defense to investigate patbophysiology of inflammatory bowel disease
| Project/Area Number |
13470249
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
FUKUSHIMA Kouhei Tohoku University, Hospital, Research Associate, 医学部附属病院, 助手 (20271900)
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| Co-Investigator(Kenkyū-buntansha) |
FUNAYAMA Yuji Tohoku University, Hospital, Lecturer, 医学部附属病院, 講師 (50192315)
SASAKI Iwao Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (60125557)
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| Project Period (FY) |
2001 – 2003
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| Keywords | intestinal flora / inflammatory bowel disease / microarray / epithelial cells / Germ-free / ulcerative colitis / Crohn's disease |
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| Research Abstract |
We identified resistin-like molecule β (RELM-β) and deleted malignant brain tumors 1(DMBT1) as molecules induced by bacterial challenge to germ-free mice and associated with mucosal defense against enteric flora. We investigated expression of those genes and proteins in mucosal tissues of experimental and human inflammatory bowel disease and induction mechanisms of the molecules.
Antibacterial activity of RELM-β
RELM-β was selectively expressed in the colon and secreted from epithelial cells into the lumen. Immunoreactive RELM-β was present in stool, suggesting possible interaction of the protein with enteric flora. We investigated whether or not RELM-β is capable of inhibiting bacterial growth against panels of enteric flora by CFU assay, resulting that this protein exhibited anti-bacterial capacity against Staphylococcus aureus.
Epithelial induction of a human homologue of murine CRP-ductin, Deleted in Malignant Brain Tumors 1 (DMBT1)
Induction of CRP-ductin mRNA was initially detected by cDNA microarray. This gene was also induced in DSS-colitis even after recovery from active inflammation by the removal of DSS. Northern blotting revealed that the human homologue, DMBT1 with 7 kb in size, was weakly expressed in control but remarkably induced in two-thirds of IBD isolates. An additional 6.5 kb band was noticed in one-third of IBD isolates. Real-time RT-PCR demonstrated that DMBT1 mRNA level was significantly higher in both DC and CD. However, qualitative difference in DMBT1 protein expression was not identified by immunohistochemistry. This gene was induced by soluble factors including IL-1β.
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Research Products
(10 results)
