| Project/Area Number |
17590906
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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 |
Neurology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
MURAKAMI Tatsufumi Kawasaki Medical School, Medicine, Associate Professor, 医学部, 助教授 (30330591)
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| Co-Investigator(Kenkyū-buntansha) |
SUNADA Yoshihide Kawasaki Medical School, Medicine, Professor, 医学部, 教授 (00240713)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | diabetic neuropathy / sensory neuropathy / gene therapy / electroporation / hypoalgesia / VEGF / P1GF2 / Neuropilin-1 / 感覚性ニィーロパチー / PIGF2 / PGF |
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| Research Abstract |
VEGF120 does not bind to neuropilin-1 (nrp-1) but binds to fetal liver kinase (flk-1) and fms-like tyrosine kinase (flt-1) receptors, while VEGF164 binds these receptors. To examine the effect of VEGF120 overexpression on sensory deficits, VEGF120 plasmid was injected into bilateral TA muscles of diabetic mice with hypoalgesia followed by electroporation. After electro-gene transfer, the nociceptive threshold on the dorsum of the hindpaw was measured bilaterally. VEGF120 gene transfer by electroporation did not significantly reduce the nociceptive threshold. To confirm the overexpression of VEGF, we measured VEGF levels in TA muscles of diabetic mice at 2 weeks after VEGF120 plasmid injection with electroporation by ELISA. There was a significant increase in the VEGF level in these samples compared with samples from diabetic mice at 2 weeks after control plasmid injection with electroporation.
Placental growth factor2 (P1GF2) has neurotrophic activity in dorsal root ganglion (DRG) neurons through nrp-1 receptor in vitro. To examine the efficiency of P1GF2 therapy for diabetic neuropathy, intramuscular P1GF2 gene transfer by electroporation was performed to treat sensory neuropathy in diabetic mice. P1GF2 was overexpressed in the TA muscles of diabetic mice with hypoalgesia, using a P1GF2 plasmid injection with electroporation. Two weeks after electro-gene transfer into the bilateral TA muscles, the elevated nociceptive threshold was significantly decreased in all treated mice. No increase in the number of endoneurial vessels in the sciatic nerve was found in the P1GF2 plasmid-electroporated mice. Taken together, these findings suggest that VEGF164 and P1GF2 electro-gene therapy significantly recovered the sensory deficits, i.e. hypoalgesia, in the diabetic mice through nrp-1 receptor in DRG neurons.
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