| Project/Area Number |
15390336
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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 |
Dermatology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SHIMIZU Hiroshi Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (00146672)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAMURA Daisuke Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (60196334)
AKIYAMA Masashi Hokkaido University Hospital, Lec., 病院・講師 (60222551)
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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 |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2003: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | wound healing / epidermolvsis bullosa / dystrophic / severe / type VII collagen / protein therapy / gene transfer / skin ulcer |
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| Research Abstract |
Type VII collagen, a non-fibrillar collagen, is a major component of anchoring fibril structures beneath the epidermal basement membrane, and is of critical importance for integrity of the cutaneous basement membrane zone. Mutations within the type VII collagen gene are associated with the dystrophic forms of epidermolysis bullosa (DEB), a group of mechanobullous diseases characterized by cutaneous fragility and tendency to form sub-basal lamina densa blisters. The patients with DEB showed delayd wound healing. The aim of this study was to clarify therapeutic effect of recombinant type VII collagen on wound healing. First, we purified a large amount of recombinant type VII collagen. We introduced the type VII collagen gene into HaCaT cells, NIH3T3 cells and 293 cells and performed selection of stable transformants by G418.293 cells expressed type VII collagen mostly among those cell lines. We could show low mobility of keratinocytes and fibroblasts from type VII collagen-gene knockout mouse and DEB patients, but addtion of recombinant type VII collagen rescued impaired mobility. Furthermore, application of recombinant type VII collagen to skin ulcer improved wound healing and we proposed type VII collagen as an anti-ulcer drug. Thus, we think that we can achieve establishment of a new strategy for treatment of wound using recombinant type VII collagen.
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