Aspirin Inhibits Fibronectin Expression and Reverses Fibronectin-Mediated Cell Invasiveness by Activating Akt...

Area of Science:

• Reproductive Biology
• Cellular Biology
• Pharmacology

Background:

• Preeclampsia is a serious pregnancy complication causing maternal organ dysfunction and fetal issues.
• Aspirin is known to reduce preeclampsia risk, but its mechanism is not fully understood.
• Fibronectin (FN) is implicated in cell motility and preeclampsia pathogenesis.

Purpose of the Study:

• To investigate the role of fibronectin (FN) in trophoblast cells and its modulation by aspirin.
• To elucidate the signaling pathways affected by FN in trophoblasts.
• To provide a potential drug mechanism for preeclampsia prevention and intervention.

Main Methods:

• Assessed cellular FN expression in placental tissues from preeclamptic patients.
• Utilized HTR-8/SVneo trophoblast cells treated with recombinant human FN (rhFN) or FN siRNA.
• Investigated the effects of rhFN and FN knockdown on trophoblast migration and invasion.
• Analyzed the activation of ERK and Akt signaling pathways.
• Examined the impact of aspirin on FN expression and FN-mediated cellular functions.

Main Results:

• Cellular FN expression was elevated in preeclamptic placentas.
• rhFN inhibited trophoblast migration and invasion, while FN knockdown facilitated these processes.
• rhFN activated ERK and Akt signaling; inhibitors rescued FN-suppressed cell motility.
• Aspirin reduced trophoblast cellular FN expression and reversed FN-induced changes in cell function and signaling.

Conclusions:

• Fibronectin significantly impacts trophoblast motility and signaling pathways (ERK/Akt).
• Aspirin exerts a protective effect by inhibiting FN expression and counteracting FN-mediated detrimental effects on trophoblast biology.
• These findings offer a potential therapeutic target and mechanism for preeclampsia intervention.