The regulation mechanism of VEGF on the expression of placental VE-cadherin through a NO-dependent signaling pathway

• Main Authors: Tung Yu Chang, 張同佑
• Other Authors: Mei Ling Tsai
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/04966818572976663305

碩士 === 國立成功大學 === 生理學研究所 === 90 === Vascular endothelial-cadherin (VE-cadheirn), a calcium-dependent homotypic adhesion molecule, is related to permeability, cell proliferation, and capillary formation. During placental development, the differentiation of trophoblasts forms vascular-like structures. VE-cadherin expresses in the intermediate and terminal villi. Vascular endothelial growth factor (VEGF), a potent vascular permeability factor or angiogenic factor, induces vascular permeability, endothelial proliferation and capillary formation by activating its two receptors (VEGFR-1 and VEGFR-2). Placenta growth factor (PlGF), a member of VEGF superfamily only binds to VEGFR-1. It is known that VE-cadherin and VEGF are related to endothelial survival. In placental tissues, VE-cadherin, VEGF, PlGF, and VEGF receptors can be detected. In particular, the protein abundance of VEGFR-1 and PlGF is greater than that of VEGFR-2 and VEGF in the placenta. Therefore, the purpose of this study was to examine whether VEGF can regulate the expression of VE-cadherin through a VEGFR-1-dependent pathway. The placenta from rats on gestation day 14 (G14), 18 (G18) and 21 (G21) were used. Placental explants from G18 rats were pretreated with various compounds in vitro for 24 hours in a 5% CO2 incubator at 37 °C. Western blot analysis measured the protein abundance of eNOS, VE-cadherin, VEGFR-1 and VEGFR-2. A NO analyzer (NOA 280 model) measured the concentration of NO in culture media. Immunoprecipitation assay was used to confirm the results of Western Blot analysis. According to the purpose, our aims were to examine: 1) the effect of pregnancy on the protein abundance of VE-cadherin, eNOS, VEGFR-1, and VEGFR-2 in placental tissues, 2) the involvement of NO in the induction of placental VE-cadherin by VEGF, and 3) the induction of VE-cadherin by PlGF through the NO signaling pathway. As our data indicate, 1) the protein profile of VE-cadherin is related to that of eNOS over gestation, 2) G18 placenta expressed the greatest amount of VEGFR-1 but the lowest amount of VEGFR-2, 3) the induction of VE-cadherin protein by VEGF can be enhanced by L-arginine, and 4) the increase of VE-cadherin protein and NO production by PlGF can be inhibited by L-NAME. In conclusion, the binding of VEGF to VEGFR-1 may increase the protein abundance through a NO-dependent pathway.