Activation of PAR-1/NADPH Oxidase/ROS Signaling Pathways is Crucial for the Thrombin-Induced sFlt-1 Production in Extravillous Trophoblasts: Possible Involvement in the Pathogenesis of Preeclampsia
| Autor: | Shi-San Liu, Qi-tao Huang, Jian-Hong Chen, Li-Lin Hang, Mei Zhong |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Small interfering RNA
Physiology sFlt-1 Enzyme-Linked Immunosorbent Assay Real-Time Polymerase Chain Reaction lcsh:Physiology Cell Line lcsh:Biochemistry chemistry.chemical_compound Thrombin Pre-Eclampsia Pregnancy medicine Humans lcsh:QD415-436 Receptor PAR-1 RNA Messenger RNA Small Interfering Vascular Endothelial Growth Factor Receptor-1 NADPH oxidase lcsh:QP1-981 biology Trophoblast Acetophenones NADPH Oxidases Trophoblasts Cell biology medicine.anatomical_structure chemistry Biochemistry embryonic structures Apocynin biology.protein Female RNA Interference Signal transduction Reactive Oxygen Species Tyrosine kinase Intracellular Signal Transduction medicine.drug |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 35, Iss 4, Pp 1654-1662 (2015) |
| ISSN: | 1421-9778 1015-8987 |
| DOI: | 10.1159/000373979 |
| Popis: | Backgrounds/Aims: Preeclampsia was characterized by excessive thrombin generation in placentas and previous researches showed that thrombin could enhance soluble Fms-like tyrosine kinase 1 (sFlt-1) expression in first trimester trophoblasts. However, the detailed mechanism for the sFlt-1 over-production induced by thrombin was largely unknown. The purpose of this study was to explore the possible signaling pathway of thrombin-induced sFlt-1 production in extravillous trophoblasts (EVT). Methods: An EVT cell line (HRT-8/SVneo) was treated with various concentrations of thrombin. The mRNA expression and protein secretion of sFlt-1 in EVT were detected with real-time polymerase chain reaction and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production were determined by DCFH-DA. Results: Exposure of EVT to thrombin induced increased intracellular ROS generation and overexpression of sFlt-1 at both mRNA and protein levels in a dose dependent manner. Short interfering RNA (siRNA) directed against PAR-1 or apocynin (an inhibitor of NADPH oxidase) could decrease the intracellular ROS generation and subsequently suppressed the production of sFlt-1 at mRNA and protein levels. Conclusions: Our results suggested that thrombin increased sFlt-1 production in EVT via the PAR-1 /NADPH oxidase /ROS signaling pathway. This also highlights the PAR-1 / NADPH oxidase / ROS pathway might be a potential therapeutic target for the prevention of preeclampsia in the future. |
| Databáze: | OpenAIRE |
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