BASIC STUDY FOR THE TREATMENT OF SKIN DISEASES USING THE REGULATION OF MATRIX METALLOPROTEINASE-9 EXPRESSION
| Project/Area Number |
15591169
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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 |
Dermatology
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
KOBAYASHI Takashi Chiba University, Clinical Biology of Extracellular Matrix, Lecturer, 医学部附属病院, 講師 (90234830)
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| Co-Investigator(Kenkyū-buntansha) |
WACHI Hiroshi Hoshi Pharmaceutical College, Clinical Chemistry, Assistant Professor, 薬学部, 講師 (50318614)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Matrix metalloproteinase-9 / Apoptosis / Differentiation / HT1080 cell / Keratinocyte / Fibroblast / Leptomycin B / Toxic epidermal necrolysis / KRE-M9 / DRF-1 / 紫外線 / UVB / Leptomycin B / Toxic epidermal necrolysis / RNAi / マトリックスメタロプロテイネイス / MMP-9 / MMP-2 / TIMP-1 / TIMP-2 / TPA responsive element |
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| Research Abstract |
Matrix metalloproteinase(MMP)-9 has been reported to play important roles in the tissue metabolism including the inflammation in many skin conditions. This project is designed because we have recently found the novel KRE-M9 element to which our designated differentiation repressing factor(DRF)-1 binds and because this mechanism is considered to be important for regulating MMP-9 expression.
1.RNAi analyses for the DRF-1 and for the MMP-9,and the effects of decoy oligonucleotides for the KRE-M9 element-Using HT1080 cells and human primary kertinocytes in culture, RNAi for MMP-9 had the effects for inhibiting apoptosis. On the other hand, RNAi for DRF-1 had the inverse effects for apoptosis. In addition, the decoy ologoncleotides for KRE-M9 induced the cells to promote the MMP-9 expression together with apoptosis.
2.Quest for the inhibitory molecules to MMP-9 expression and the appplication for disease models-Leptomycin B, which regulates nucleo-cytoplasmic trafficking of not a few proteins including transcription factor-related ones, showed the effects for upregulation not of MMP-2,but of MMP-9 expression by promoting its transcription for which KRE-M9 as well as the other elements is shown to be responsible. In addition, its topical application brought the UVB-irradiated skin of mouse the improvement of epidermal dyskeratosis together with the inflammatory infiltrates both in the dermis and in the subcutaneous fat tissue.
3.Survey for MMP-9 expression in the skin conditions-1)The high levels of MMP-9 expresion were detected in the serum of the patient with toxic epidermal necrolysis. 2)Gelatinolytic activities were detected in the dyskeratotic lesions in squamous cell carcinoma. 3)Not only MMP-2,but also MMP-9 was detected from human fibroblasts in culture by the inflamatory cytokines.
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Report
(3 results)
Research Products
(23 results)
