PADI1 aggravates endoplasmic reticulum stress in trophoblast cells by inhibiting the FAK-ERK signaling pathway.

Preeclampsia (PE) is a multisystemic syndrome of pregnancy that seriously affects maternal and infant healthcare. Here, we identified PADI1 as an abnormally highly expressed gene in PE and investigated its effect on trophoblast cells. According to the analysis results from GEO datasets GSE186257 and GSE143953, PADI1 is highly expressed in the placental samples of PE patients. PADI1 knockdown promoted the growth and migration of trophoblast cells. HTR-8 and Swan-71 cells were treated with 200 nmol/L TG to simulate ERS in vitro. PADI1 knockdown inhibited TG-induced ERS and apoptosis. Mechanistically, PADI1 knockdown downregulated ERS-related factors including IRE1α, XBP1, CHOP, ATF6 and GRP78. The FAK/ERK1/2 signaling pathway has been identified as a downstream target of PADI1 in trophoblast cells. Inhibition of FAK/ERK1/2 effectively hindered the enhancement of cell activity by PADI1 knockdown in TG-treated trophoblast cells. In conclusion, PADI1 was highly expressed in the placental tissues of PE patients. PADI1 knockdown inhibited the ERS-induced apoptosis in trophoblast cells through FAK/ERK1/2 signaling pathway, suggesting the potential role of PADI1 in PE prevention and treatment.