Increased Expression Of Fatty Acid Binding Protein 4 In Preeclamptic Placenta And Its Relevance To Disease

BackgroundPreeclampsia affects 2-8% of nulliparous pregnancies and is one of the major causes for maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction [1-3]. Abnormal placentation due to the abnormal function of trophoblastic cell and inadequate maternal response to trophoblast invasion has been regarded as the critical initial pathology of preeclampsia [4]. In normal development of the placenta, extravillous trophoblasts invade the muscular layer of spiral arteries, and this leads to the remodeling of maternal spiral artery [1-3,5-8]. In preeclampsia, incomplete invasion of trophoblasts into the maternal spiral arteries and inadequate proliferation of non-invading trophoblasts with multiple nuclei in the interstitial space were observed [1-2,4,9]. Excessive proliferation of placental trophoblast has been found in the placenta of preeclampsia [10-12]. However, the mechanisms behind the abnormal function of tropoblast remain unclear. Previously, we described that maternal serum level of FABP4 was significantly increased in preeclamptic women compared with normal pregnant women [13]. Scifres et al further observed that maternal serum FABP4 levels were elevated before the clinical onset of preeclampsia, and this increase occurs independently of maternal body mass index [14].These findings implicate that FABP4 plays a role in the development of preeclampsia. FABP4 was expressed in placental trophoblast, and hypoxia, a pathological characteristic of preeclampsia, induced the expression of FABP4 via hypoxia inducible factors (HIF) 1α and 2a [6,15-16]. However, it remains unknown if placental expression of FABP4 is elevated in preeclampsia and if the elevation of circulating FABP4 is associated with altered expression of FABP4, and also little is known if FABP4 regulates the biological function of trophoblast cell.ObjectivesTo determine the expression of FABP4 in placenta of women with preeclampsia and normal pregnancy, and to delineate the regulatory effects on thophoblast cell by FABP4.MethodsThe expression of FABP4 was determined by real-time PCR for mRNA or Western blotting for protein. Interference of small ribonuclear acid (siRNA) and specific FABP4inhibitor were used to inhibit FABP4. The proliferation, migration and invasion of epithelial cells were evaluated with CCK-8assay, wound-healing test and transwell analysis respectively.ResultsThe expression of FABP4 was significantly higher in the placenta of preeclamptic women than that of women with normal pregnancy (t=4.244, P<0.001). FABP4 siRNA significantly reduced the proliferation of trophoblast (P<0.001). The specific inhibition of FABP4 inhibited the preoliferation of trophoblast in a dose-dependent manner (P<0.001) and the inhibitory effect increased as the concentration of inhibitor increased. FABP4 siRNA and specific inhibitor significantly decreased the migration (P<0.001) and invasiveness (P<0.001) of trophoblast.Conclusions The increase in placental FABP4 expression in preeclampsia may affect the function of trophoblast.