2006 Fiscal Year Final Research Report Summary
Structure and function of VEGF receptors related to preeclampsia.
| Project/Area Number |
17390110
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SHIBUYA Masabumi The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (10107427)
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| Project Period (FY) |
2005 – 2006
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| Keywords | angiogenesis / VEGF / VEGF receptor / renal dysfunction |
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| Research Abstract |
Preeclampsia is a major disease in gynecological field. Recent studies strongly suggest that soluble form of Flt-1 (sFlt-1/sVEGFR1) is deeply involved in this disease. We attempted to understand the whole functions of Flt-1 protein including sFlt-1.
1, We found that trophoblast stem cell (TS cell) system could be a good model for flt-1 gene expression, since in placenta, trophoblast cells are the major producer for sFlt-1. During the differentiation, flt-1 mRNA was 5-fold elevated, suggesting a physiological gene expression. However, we could not find a stress which abnormally upregulate the expression of sflt-l. Such a stress could be a candidate for inducer of preeclampsia.
2, We examined the effect of exogenous VEGF-A and sFlt-1 on pregnant mice. We found that exogenous VEGF-A induces pathological change at placenta such as fibrin deposition, and exogenous sFlt-1 transiently induces hypertension and proteinurea. However, to maintain these phenotypes, a large amount of sFlt-1 appears to be required.
3, sFlt-1 protein efficiently blocked abnormally secreted VEGF-A from ascites tumors, resulting in suppression of ascites volume and tumor growth in ascites. Thus, sFlt-1 protein is a good candidate for an inhibitor of pathological VEGF-A and ascites tumor.
4, Flt-1 signaling-deficient mice (Flt-1 TK-/- mice) showed a milder phenotype in arthritis-model, indicating that tyrosine kinase of Flt-1 is a new target for the treatment of rheumatoid arthritis.
Dr.Ambati' s group collaborating with us found that sFlt-1 is an important natural molecule for maintaining avascularity in cornea.
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[Journal Article] Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocyte/macrophages2006
Author(s)
Murakami, M., Iwai, S., Hiratsuka, S., Yamauchi, M., Nakamura, K., Iwakura, Y., Shibuya, M.
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Journal Title
Blood 108
Pages: 1849-1856
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Corneal avascularity is due to soluble VEGF receptor-1.2006
Author(s)
Ambati BK, Nozaki M, Singh N, et al., Khurana TS, Shibuya M, Baldwin ME, Ferrara N, Gerber HP, De Falco S, Witta J, Baffi JZ, Raisler BJ, Ambati J.
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Journal Title
Nature 443
Pages: 993-997
Description
「研究成果報告書概要(欧文)」より
