Fas regulates the apoptosis and migration of trophoblast cells by targeting NF‑κB

Abstract

Placental trophoblast apoptosis is a major pathological feature of preeclampsia. Fas has been reported to be highly expressed in the placentas of patients with preeclampsia. However, the role and underlying mechanisms of Fas in the pathogenesis of preeclampsia have not been elucidated. In the present study, the expression of Fas in JAR human choriocarcinoma cells was overexpressed and knocked down to determine the function and possible mechanism of Fas in trophoblast cells in the progression of preeclampsia. The results of flow cytometry, Cell Counting Kit-8 and Transwell assays indicated that the overexpression of Fas promoted apoptosis, suppressed viability and impaired the migration of the human trophoblast cells. In addition, western blotting revealed that the overexpression of Fas increased the expression of nuclear factor kB (NF-kB), Bax, tumor necrosis factor α (TNF-α) and interleukin-2 (IL-2), and decreased the expression of Bcl-2 at the protein level in trophoblast cells. By contrast, the knockdown of Fas decreased the apoptosis of trophoblast cells and increased their viability and migration. In addition, the knockdown of Fas suppressed the expression of NF-κB, Bax, TNF-α and IL-2, and increased the expression of Bcl-2. Notably, the overexpression of NF-κB p65 attenuated the Fas knockdown-induced inhibition of apoptosis and acceleration of migration of the trophoblast cells. The overexpression of NF-κB in trophoblast cells also reversed the reduction in Bax expression and increase in Bcl-2 expression induced by Fas knockdown in trophoblast cells. These results indicate that Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB, which suggests that the silencing of Fas is a promising therapeutic strategy for preeclampsia.

CircACLY regulates proliferation, differentiation and apoptosis of Jingyuan chicken myoblasts by sponging gga-miR-6660-3P

“…Downregulation of MyoD mediates the expression of miR-1 and miR-206, activates transcription of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and B-cell lymphoma-extra large (BCL-xL), and enhances myoblast survival [41]. Apoptosis is an active process of programmed death that involves the activation, expression and regulation of a series of genes, including BAK1, BID, FAS, and Caspase9 [42][43][44]. The apoptosis-promoting BAK1 and BID proteins can commit a cell to programmed death by permeabilizing the outer mitochondrial membrane (OMM) and subsequently initiating the caspase cascade [42,45].…”

Evaluation of the Effect of the Fibroblast Growth Factor Type 2 (FGF-2) Administration on Placental Gene Expression in a Murine Model of Preeclampsia Induced by L-NAME

“…The increase in the p53 expression corresponds to the hypoxia that is generated in the placenta by PE, at least in vitro [ 52 ], and has implications in the intrauterine growth restriction [ 53 ]. The FAS, on the other hand, is involved in mediating the maternal immune response, in cell remodeling, and in cell proliferation [ 51 , 54 ]; therefore, the increase in this protein is a direct indicator of placental apoptosis, which is a common finding in PE [ 55 , 56 ]. Although these findings are not completely comparable with ours, the under expression of the apoptosis-related genes may be due to the fact that the placental biopsies that were used in this study came from the rats that were at the end of their pregnancy.…”

Paeonol alleviates placental inflammation and apoptosis in preeclampsia by inhibiting the JAK2/STAT3 signaling pathway

“…Bcl‐2 is an antiapoptotic protein, the elevated level of which implies the promotion of cell apoptosis. Therefore, the degree of apoptosis can be directly reflected by the changed levels of Bcl‐2 and Bax 35 . Caspase‐3 belonging to the protease family exerts crucial functions in both extrinsic and intrinsic apoptotic processes 36 .…”

“…Therefore, the degree of apoptosis can be directly reflected by the changed levels of Bcl-2 and Bax. 35 Caspase-3 belonging to the protease family exerts crucial functions in both extrinsic and intrinsic apoptotic processes. 36 It has been reported that Pae could inhibit cell apoptosis in high glucose and palmitic acid-induced endothelial cells 37 and Pae activates the class III PI3K/Beclin-1 pathway to inhibit apoptosis of vascular smooth muscle cells.…”