1998 Fiscal Year Final Research Report Summary
Roles of Matrix Metalloproteinases in wound healing and neovascuarization
| Project/Area Number |
09670220
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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 |
Experimental pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OKADA Akiko Univ.of Tokyo, Inst.of med.Sci., Assistant Prof., 医科学研究所, 助手 (00233320)
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| Project Period (FY) |
1997 – 1998
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| Keywords | wound healing / neovascularization / matrix metalloproteinase / MMP inhibitor / skin / knockout mice |
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| Research Abstract |
Skin wound healing depends on cell migration and extracellular matrix remodeling. Both processes, which are necessary for reepithelization and restoration of the underlying connective tissue, are believed to involve the action of extracellular proteinases. We screened cDNA libraries and found that six matrix metalloproteinase genes were highly expressed during rat skin wound healing.
GelatinaseA (GelA) and membrane-type 1 matrix metalloproteinase (MT1-MMP) transcripts were expressed in stromal cells. The detection of high levels of the mature GelA form in the granulation tissue but not in the regenerating epidermis, suggest that MT1-MMP and GelA contribute to the restoration of connective tissue and neovascularization during rat skin wound healing. Furthermore, we showed that TIMP-2 is necessary for activation of pro-GelA by MT1-MMP using agarose beads model. We now make knock-out mice of MT1-MMP gene. Already we have obtained GelA knock-out mice, and we are under studying on the differences of wound healing and neovascular process between normal mice and knock-out mice. We also study on the effect of synthetic MMP inhibitor to wound healing process and/or neovascularization.
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[Publications] Kusagawa, H., Onoda, K., Namikawa, S., Yada, I., Okada, A., Yashida, T., Sakakura, T.: "Expression and degeneration of tenascin-C in human lung cancers." Br.J.Cancer. 77 :. 98-102 (1998)
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