| Co-Investigator(Kenkyū-buntansha) |
AKITA Sadanori Nagasaki University, Medical School Hospital, assistant professor, 医学部・附属病院, 助手 (90315250)
HIRANO Akiyoshi Nagasaki University, School of Medicine, associate professor, 医学部, 助教授 (90208835)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2000: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1999: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Research Abstract |
Among molecular biological analysis for wound healing, keloid represents the abnormal wound healing pattern. Keloid most abundantly expresses the insulin-like growth factor-1, IGF-1 as confirmed by degenerative receptor tyrosine kinase assay. IGF-1 involves in the invasiveness of keloid via post-receptor signal transduction. Moreover, keloid resists the ceramide-induced apoptosis. Ceramide normally induces the fibroblast apoptosis in dose-dependent and in time-dependent manner ; however, fibroblasts derived from keloid showed the G2 arrest by FACS cell sorter and confirmed by reduced cell number by WST-1 assay. When IGF-1 added, keloid fibroblasts resist the ceramide-induced apoptosis. This was positively correlated with IGF-1 receptor expression level. PI-3 inhibitor, Wortmaninn pre-treatment, was markedly abolished inhibition of apoptosis via IGF-1 signaling.
On the other hand, on behalf of prolonged skin allograft survival, the effective modalities such as cytokine gene therapy were tested. In between BALB/c and B6D2F1 strain mice, Leukemia Inhibitory Factor, LIF plasmid cDNA was injected into the skin allograft donor. LIF expressions were observed in 24 hours and 21 days post-transplantation. The gp130, signal-transduction component of LIF, was expressed along with LIF.When B6D2F1 to BALB/c skin allografting, helper T type2 cytokine (IL-10) was observed, thus immune tolerance was indicated for skin allografting in LIF gene therapy.
In bone metabolism, LIF was tested in the cranial bone defect model. LIF was efficiently enhanced the bone formation via osteocyte activation.
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