FOXO1 modulates the biofunctions of trophoblast cells in preeclampsia via the DUSP9/p38/JNK signaling pathway

Preeclampsia (PE) is currently one of the major causes of health threats and can lead to maternal and fetal death. The onset of PE is attributed to cellular dysfunction resulting from disruption of the molecular regulatory network in trophoblast cells. We discovered that FOXO1 was downregulated in the placentas of patients with preeclampsia. To elucidate the involvement of FOXO1 in the development of preeclampsia, we generated trophoblast cell lines with manipulated levels of FOXO1, either through overexpression or knockdown, to elucidate its biological function and underlying mechanisms. FOXO1 expression is positively correlated with the invasive, migratory, and proliferative abilities of trophoblast cells. Transcriptome sequencing analysis revealed that DUSP9 is a potential target gene of FOXO1. The suppression of DUSP9 expression markedly diminishes the invasive, migratory, and proliferative abilities of trophoblast cells. Silencing DUSP9 in trophoblast cells with elevated FOXO1 levels can attenuate their physiological functions. We found that overexpression/inhibition of FOXO1 can correspondingly suppress/activate the p38/JNK signaling pathway. Notably, the inhibition of DUSP9 in the context of FOXO1 overexpression can activate the p38/JNK signaling pathway. FOXO1 modulates the biological functions of trophoblast cells in preeclampsia via the DUSP9/p38/JNK signaling pathway.