| Project/Area Number |
13670832
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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 |
Pediatrics
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| Research Institution | Jichi Medical School |
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Principal Investigator |
GUNJI Yuji Jichi Medical School, Pediatrics, Lecturer, 医学部, 講師 (90245043)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAUCHI Tadahiko Jichi Medical School, Pediatrics, Assistant Lecturer, 医学部, 助手 (20271223)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Tie2 / Survival signaling / Vascular endothelial cell / Lymphoid endothelial cell / Cord blood / Pediatric malignancy / Akt / KIT / Cbl / Ubiquitination |
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| Research Abstract |
The endothelial cell-specific receptor tyrosine kinase Tie-2 is thought to have an important role in the establishment maintenance and regression of vascular structures around the malignant tumors. The Akt sorine/threonine kinase was also reported to have an essential role in vascular development via the inhibition of programmed cell death. Previously, we demonstrate that activated Tie2 associates with B-Raf and induces its tyrosyl phosphorylation, resulting in increased B-Raf kinase activity and resulted in survival of endothelial cells in addition to Akt. In this study, we looked into the downstream molecules of Tie2/Akt. We could not detect the phosphorylation of Bad or FKRH proteins, although the Akt was well phosphorylated at serine 473.These findings suggest that other molecules like caspase9 might be downstream molecules. ****stingly, Akt phosphorylation induced by activated Tie2 mutants (R849W) was less than one induced by Tie2.These finding might explain the mechanisms of the
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disease of venous malformation.
In addition to these studies, we studied ontogeny-related differences in vascular endothelial precursors in cord blood (CB) at different gestational weeks, and we report striking differences between findings at different gestational weeks, especially before and after 35 weeks. Endothelial cells have been reported to express CD34 and KIT. Our phenotypic analysis showed that CD34+ CB cells in the early gestational weeks contained more of the KITlow/-fraction than the KIThigh fraction. In BM,about 40% of CD34+ ceils were KITlow/-. In contrast, 55.5% (mean) and 76.3% of the CD34+ cells were KITlow/- in the early and in the later gestational weeks. We also detected about 10% of CD34+ cells express flt4 which is thought to be a maker of lymphoid endothelial cells.The existence of vascular and lymphoid endothelial cells or precursors in CB cells in premature infants may be an important source that could be helpful in gaining new insights into the biology of early endothalial precursors and in studying developmental change in the human vascular system. Less
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