| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2006: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
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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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