Growth differentiation factor 9 inhibits vascular endothelial growth factor expression in human granulosa cells

Growth differentiation factor 9 inhibits vascular endothelial growth factor expression in human granulosa cells
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生长分化因子 9 抑制人颗粒细胞中血管内皮生长因子的表达

DOI:
10.1080/09513590.2020.1718640
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发表时间:
2020-01
影响因子:
2
通讯作者:
周灿权
周灿权
中科院分区:
医学4区
文献类型:
--
作者:
郭聪聪;陈明晖;马文敏;蔡炳;徐艳文;钟依平;周灿权

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在主动脉内皮细胞中,转化生长因子β信号通路参与了血管内皮生长因子的调节,血管内皮生长因子编码了一种对卵巢过度刺激综合征的发生至关重要的血管生成因子。生长分化因子9(GDF9)是转化生长因子β家族的成员,其对人颗粒细胞中VEGFmRNA表达的影响尚不清楚。本研究从体外受精患者取卵过程中采集的人颗粒细胞进行体外培养。培养48 h后,用不同剂量的GDF9加或不加碱性磷酸酶抑制剂SB431542。收集培养上清液,用酶联免疫吸附试验测定血管内皮细胞生长因子的浓度。收集并提取细胞RNA,用实时荧光定量聚合酶链式反应进行定量。我们的研究表明,GDF9以剂量依赖的方式抑制人颗粒细胞释放血管内皮生长因子,并下调这些细胞中VEGFmRNA的水平。此外,SB431542可拮抗GDF9对VEGFmRNA的抑制作用,并减弱GDF9对人颗粒细胞释放VEGF的抑制作用。结果表明,GDF9可抑制人颗粒细胞中VEGFs的表达,Alk5可能参与了这一过程。
In aortic endothelial cells, the TGFβ signaling pathway is involved in the regulation of vascular endothelial growth factor (VEGF), which encodes a potent angiogenic factor crucial for the development of ovarian hyperstimulation syndrome. Growth differentiation factor 9 (GDF9) is a member of the TGFβ family and its effect onVEGFexpression in human granulosa cells is unknown. In this study, human granulosa cells were collected from patients during the course of oocyte retrieval forin vitrofertilization and were culturedin vitro. After the first 48 h of culture, cells were treated with GDF9 with or without SB431542 (an ALK5 inhibitor) at various doses. The medium was then collected to determine the concentration of VEGF by ELISA. Cellular RNA was collected and extracted for quantification by real-time quantitative fluorescence PCR. Our study showed that GDF9 suppressed VEGF release from human granulosa cells in a dose-dependent manner and also downregulatedVEGFmRNA levels in these cells. Furthermore, SB431542 antagonized the suppression ofVEGFmRNA by GDF9 and diminished the inhibitory effect of GDF9 on VEGF release by human granulosa cells. Our results indicated that GDF9 can inhibitVEGFexpression in human granulosa cells and ALK5 might mediate this process.
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