| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Outline of Final Research Achievements |
Versican is a large proteoglycan expressed at high levels in tissues during development and remodeling in pathological conditions. Its core protein is cleaved at a region close to the N-terminal end of CSbeta domain by ADAMTS family proteinases. Here, using a CRISPR/Cas9 system, we generated knock-in mice (V1R), which express an ADAMTS cleavage-resistant versican. Some V1R homozygote mice, termed R/R, exhibit syndactyly and organ hemorrhage at late embryonic stages. In wound healing experiments, R/R wound shows versican accumulation and activated TGFbeta-signaling in the early stage, leading to faster healing than wild type wound. The wound region showed higher levels of overall cell proliferation including endothelial cells and myofibroblasts, and increased levels of inflammatory cell infiltration. These results demonstrate that the cleavage site determines versican turnover and that versican plays a central role in the provisional matrix during the wound repair.
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