Role of extracellular signal-regulated kinase and AKT cascades in regulating hypoxia-induced angiogenic factors produced by a trophoblast-derived cell line
| Autor: | Hekiko Soen, Akiko Tanabe, Yoshiki Yamashita, Tatsuharu Sekijima, Masahide Ohmichi, Yoshito Terai, Daisuke Fujita, Keijirou Narahara, Hideki Kamegai |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Endocrinology Diabetes and Metabolism Gene Expression Syncytiotrophoblasts Receptors Cell Surface Biology Protein Serine-Threonine Kinases Transfection Cell Line chemistry.chemical_compound Endocrinology Antigens CD Internal medicine Cell Line Tumor medicine Homeostasis Humans Choriocarcinoma RNA Messenger RNA Small Interfering Extracellular Signal-Regulated MAP Kinases Protein kinase B Protein Kinase Inhibitors Cytotrophoblast TOR Serine-Threonine Kinases Endoglin Intracellular Signaling Peptides and Proteins Trophoblast Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Trophoblasts Vascular endothelial growth factor Enzyme Activation Oxygen HIF1A medicine.anatomical_structure chemistry Gene Expression Regulation embryonic structures Angiogenesis Inducing Agents Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | The Journal of endocrinology. 206(1) |
| ISSN: | 1479-6805 |
| Popis: | During human pregnancy, trophoblasts play an important role in embryo implantation and placental development. Cytotrophoblast cells invade the uterine spiral arteries and differentiate into extravillous trophoblasts, resulting in the remodeling of the uterine vessels and fetoplacental vasculature. During early pregnancy, a physiologically hypoxic environment induces the production of angiogenic factors, such as vascular endothelial growth factor (VEGF), which are suggested to locally control the vascular remodeling. Endoglin, a cell-surface coreceptor for transforming growth factor-β1, is highly expressed in endothelial cells and syncytiotrophoblasts, and can be associated with endothelial nitric oxide synthase and vascular homeostasis. Several studies have recently suggested that some pregnancy-related complications, such as preeclampsia, have their origins early in pregnancy as a result of abnormalities in implantation and placental development. Although angiogenic factors are recognized as key molecules in placental development, little is known about the mechanism(s) of their regulation in trophoblasts. In this study, we elucidated the mechanisms underlying the regulation of VEGF and endoglin production under hypoxic conditions in the trophoblast-derived cell line, BeWo. We evaluated the role of the AKT–MTOR cascade and ERK kinase in the expression of VEGF and endoglin in response to hypoxia using various kinase inhibitors and small interfering RNA targeted against hypoxia-inducible factor (HIF)-1α (listed as HIF1A in Hugo Database). Our results suggest that both the phosphatidylinositol 3-kinase–AKT–MTOR–HIF-1α and ERK–HIF-1α signaling pathways are crucial for increasing VEGF and endoglin expression in response to hypoxia in BeWo cells. |
| Databáze: | OpenAIRE |
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