Excess fibronectin 1 participates in pathogenesis of pre-eclampsia by promoting apoptosis and autophagy in vascular endothelial cells

Abstract

Abstract Plasma fibronectin 1 (FN1) levels are elevated in individuals with pre-eclampsia (PE), which may be applied as a possible b marker for vascular endothelial injury during PE. In the present study, the possible role of FN1 in the pathogenesis of PE and regulation of apoptosis and autophagy in vascular endothelial cells was explored. Plasma FN1 levels in 80 patients with PE and 40 healthy pregnant individuals were measured using ELISA to verify its relationship with the severity of PE. pcDNA3.1-FN1 or FN1-small interfering (si) RNA was used to manipulate the expression of FN1 in human umbilical vein endothelial cells (HUVECs) to assess the effects of FN1 on cell apoptosis, autophagy, and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. It was found that upregulation of FN1 promoted apoptosis and autophagy, in addition to significantly inhibiting the activation of AKT and mTOR in HUVECs. By contrast, downregulation of FN1 expression inhibited cell apoptosis and autophagy, but increased AKT and mTOR phosphorylation in HUVECs that were cultured in serum samples obtained from patients with PE. Rescue experiments found that the PI3K/AKT inhibitor LY294002 reversed the effects of FN1-siRNA on apoptosis and autophagy in HUVECs cultured in serum from patients with PE. Therefore, data from the present study suggest that FN1 participates in the pathogenesis of PE by promoting apoptosis and autophagy in vascular endothelial cells, which is associated with the PI3K/AKT/mTOR signaling pathway.