Effect of heparin-binding EGF-like growth factor and amphiregulin on the MAP kinase-induced production of vascular endothelial growth factor by human granulosa cells
Effect of heparin-binding EGF-like growth factor and amphiregulin on the MAP kinase-induced production of vascular endothelial growth factor by human granulosa cells
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DOI：
10.3109/08977194.2011.607136
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发表时间：
2011-12-01
期刊：
影响因子：
1.8
通讯作者：
Narahara, Hisashi
中科院分区：
文献类型：
--
作者：
Karakida, Sinya;Kawano, Yasushi;Narahara, Hisashi
颗粒细胞的功能受多种激素和生长因子的调控。我们的目的是阐明肝素结合egf样生长因子（HB-EGF）和双调节蛋白（AR）在人颗粒细胞系KGN中诱导血管内皮生长因子（VEGF）产生的调控。将KGN细胞与HB-EGF和AR孵育24 h，采用酶联免疫吸附法测定培养基中VEGF的水平。Western blot检测KGN细胞中MAP激酶的活化情况。单独使用HB-EGF或AR可显著增加VEGF的产生，且呈剂量依赖性，而AG1478或U0126可降低VEGF的产生。经HB-EGF或AR处理后，MAP激酶活性增加，提示HB-EGF和AR诱导VEGF的机制与MAP激酶有关。VEGF的增加可能有助于新生血管的形成，从而促进各种排卵现象和卵泡的生长。
The function of granulosa cells is regulated by various hormones and growth factors. Our aim is to clarify the regulation of vascular endothelial growth factor (VEGF) production induced by heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR) in a human granulosa cell line, KGN. KGN cells were cultured and incubated for 24 h with HB-EGF and AR. The levels of VEGF in the culture media were measured by an enzyme-linked immunosorbent assay. The activation of MAP kinase in KGN cells was detected by Western blot analysis. VEGF production was significantly increased by HB-EGF or AR alone in a dose-dependent manner, whereas it was decreased by AG1478 or U0126. The MAP kinase activity was increased by treatment with HB-EGF or AR. The results suggested that VEGF is induced by HB-EGF and AR through mechanisms involving MAP kinase. The increase in VEGF may contribute to neovascularization, which in turn would promote various ovulation phenomena as well as follicular growth.