2010 Fiscal Year Final Research Report
Elucidation of functional roles of new genes in angiogenesis
| Project/Area Number |
20590273
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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 |
General medical chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
EMA Masatsugu University of Tsukuba, 大学院・人間総合科学研究科, 講師 (60359578)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Satoru 筑波大学, 大学院・人間総合科学研究科, 教授 (50271896)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 循環器 / 転写因子 / 発生 / 再生 |
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| Research Abstract |
Blood vessels are therapeutic targets for cancer, ischemic diseases and diabetes-related diseases. Therefore, understanding the process of angiogenesis is important for not only intellectual but potentially development of medicine for such diseases. We identified that PLVAP and a novel SH2-related genes as endothelial-specific genes in a previous studies. So, we thought that elucidation of the molecular functions of PLVAP and SH2-related genes during embryogenesis and tumor angiogenesis leads us development of new therapeutic methods for cancer and regenerative medicine. Goals of this study are (1) understanding of the physiological functions of PLVAP and the SH2-related gene during mouse development, (2) understanding of the physiological functions of PLVAP and the SH2-related gene during tube formation in vitro using HUVEC (human umbilical vein endothelial cells), (3) understanding of the physiological functions of PLVAP and the SH2-related gene during tumor angiogenesis. Although the targeting vectors for PLVAP and the SH2-related gene were constructed and electroporated into ES cells, no homologous recombinant was obtained. In order to investigate the physiological functions of PLVAP and the SH2-related gene, knock-down oligonucleotides were introduced into HUVEC. The tube formation was visualized by iolectinB4-FITC staining and evaluated by a software analysis. The knock-down of PLVAP and SH-related gene clearly showed that they are important for the network formation of endothelial cells. When mRNA expressions were investigated in human glioblastomas and astrocytomas, glioblastomas expressed human homologs of PLVAP and the SH2-related gene, indicating that they are expressed abundantly in tumor endothelial cells.
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