Effect of Eicosapentaenoic Acid on sFlt-1 and HIF-1α Expression Under Induced Hypoxia Conditions in Trophoblast Tumor Cell Line (JEG-3)

Abstract

Background: Previous studies have shown the altered levels of long-chain polyunsaturated fatty acids (LCPUFAs) in pathological hypoxic conditions. Elevated soluble fms-like tyrosine kinase-1 (sFlt-1) expression in hypoxia plays an important role in the pathogenesis of placental as preeclampsia. Objectives: The eicosapentaenoic acid (EPA; 20:5, n-3) as LCPUFAs (omega-3) might attenuate sFlt-1 and hypoxia-inducible factor-1α (HIF-1α) expressions and secretions. Methods: JEG-3 cells were incubated with dimethyloxalylglycine (DMOG) and EPA. The SFlt-1 gene expression was determined using a real-time polymerase chain reaction. The protein secretion of sFlt-1 and HIF-1α were analyzed using Western blot. Results: The incubation of JEG-3 cells with DMOG significantly elevated messenger ribonucleic acid (mRNA) expression and protein secretion of sFlt-1 (P < 0.05); nevertheless, EPA decreased mRNA expression and protein secretion of sFlt-1 (P < 0.05). Moreover, EPA inhibited the effect of DMOG on sFlt-1 (P = 0.0361) gene expression and protein secretion and HIF-1α (P = 0.0241) protein secretion. Conclusions: The sFlt-1 expression decreased by n-3 fatty acids in trophoblast tumor cell line under induced hypoxia conditions. It seems that changes in sFlt-1 expression are mediated by the transcription factor HIF-1α.