Upregulation of angiogenic factors via protein kinase c and hypoxia-induced factor-1a pathways under high-glucose conditions in the placenta

Takashi Mitsui, Kazumasa Tani, Jota Maki, Takeshi Eguchi, Shoko Tamada, Eriko Eito, Kei Hayata, Hisashi Masuyama

Research output: Contribution to journalArticle

Abstract

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-1a (HIF-1a) and protein kinase Cß (PKCß) 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-1a, 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-1a, 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 PKCß and HIF-1a pathways, suggesting their involvement in PE pathogenesis.

Original languageEnglish
Pages (from-to)359-367
Number of pages9
JournalActa Medica Okayama
Volume72
Issue number4
Publication statusPublished - Jan 1 2018

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Angiogenesis Inducing Agents
Protein Kinases
Placenta
Up-Regulation
Glucose
Protein Kinase C
Pre-Eclampsia
Vascular Endothelial Growth Factor Receptor-1
Choriocarcinoma
Control Groups
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
Hypoxia
Enzyme-Linked Immunosorbent Assay
Cells
Cell Line
Trophoblasts
Metabolism
Real-Time Polymerase Chain Reaction
Chemical activation

Keywords

  • High-glucose condition
  • Preeclampsia
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Upregulation of angiogenic factors via protein kinase c and hypoxia-induced factor-1a pathways under high-glucose conditions in the placenta",
abstract = "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-1a (HIF-1a) and protein kinase C{\ss} (PKC{\ss}) 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-1a, 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-1a, 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 PKC{\ss} and HIF-1a pathways, suggesting their involvement in PE pathogenesis.",
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T1 - Upregulation of angiogenic factors via protein kinase c and hypoxia-induced factor-1a pathways under high-glucose conditions in the placenta

AU - Mitsui, Takashi

AU - Tani, Kazumasa

AU - Maki, Jota

AU - Eguchi, Takeshi

AU - Tamada, Shoko

AU - Eito, Eriko

AU - Hayata, Kei

AU - Masuyama, Hisashi

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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-1a (HIF-1a) and protein kinase Cß (PKCß) 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-1a, 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-1a, 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 PKCß and HIF-1a pathways, suggesting their involvement in PE pathogenesis.

AB - 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-1a (HIF-1a) and protein kinase Cß (PKCß) 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-1a, 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-1a, 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 PKCß and HIF-1a pathways, suggesting their involvement in PE pathogenesis.

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