Upregulation of Angiogenic Factors via Protein Kinase C and Hypoxia-induced Factor-1α Pathways under High-glucose Conditions in the Placenta.
Upregulation of Angiogenic Factors via Protein Kinase C and Hypoxia-induced Factor-1α Pathways under High-glucose Conditions in the Placenta.
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DOI：
10.18926/amo/56171
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发表时间：
2018
影响因子：
0.5
通讯作者：
T. Mitsui;Kazumasa Tani;Jota Maki;Takeshi Eguchi;Shoko Tamada;Eriko Eto;K. Hayata;H. Masuyama
中科院分区：
文献类型：
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作者：
T. Mitsui;Kazumasa Tani;Jota Maki;Takeshi Eguchi;Shoko Tamada;Eriko Eto;K. Hayata;H. Masuyama
妊娠期糖代谢异常是先兆子痫（PE）的既定危险因素。胎盘血管生成因子之间平衡的破坏与PE病理生理学有关。我们在体外研究了低氧诱导因子-1 α（HIF-1α）和蛋白激酶Cβ（PKCβ）是否参与高糖条件下胎盘血管生成因子的调节。将人绒毛膜癌细胞系BeWo和JEG-3以及人滋养层细胞系HTR-8/SVneo分别用10和25 mmol/L葡萄糖[对照葡萄糖组（CG）和高糖组（HG）]培养。采用实时荧光定量PCR和ELISA检测CG和HG中HIF-1α、可溶性fms样酪氨酸激酶-1（sFlt-1）、胎盘生长因子（PlGF）和血管内皮生长因子（VEGF）的表达变化。还通过ELISA测量PKC活化。HIF-1α、sFlt-1、PlGF和VEGF在高血压组的表达明显高于对照组。PKC活性在高糖组明显升高。高糖通过PKCβ和HIF-1α途径影响绒毛膜癌细胞血管生成因子的表达，提示其参与PE的发病机制。
Abnormal glucose metabolism during pregnancy is an established risk factor for preeclampsia (PE). Disruption of the balance between placental angiogenic factors is linked to PE pathophysiology. We examined whether hypoxia-induced factor-1α (HIF-1α) and protein kinase Cβ (PKCβ) are involved in the regulation of placental angiogenic factors under high-glucose conditions in vitro. The human choriocarcinoma cell lines BeWo and JEG-3, and the human trophoblast cell line HTR-8/SVneo were cultured with 10 and 25 mmol/L glucose [control glucose group (CG) and high-glucose group (HG), respectively]. We examined the changes in HIF-1α, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) expression in the CG and HG by real-time PCR and ELISA. PKC activation was also measured by ELISA. The expressions of HIF-1α, sFlt-1, PlGF, and VEGF were significantly higher in the HG than in the CG. PKC activity was significantly increased in the HG. High glucose affected the expression of angiogenic factors in choriocarcinoma cells via the PKCβ and HIF-1α pathways, suggesting their involvement in PE pathogenesis.