FAK regulates trophoblast functions of invasion and proliferation through Rap1 pathway in early-onset preeclampsia.

Abstract

This investigation examined focal adhesion kinase (FAK)'s role in trophoblast cellular processes during early-onset preeclampsia (EOPE). We analyzed FAK and its phosphorylated form (pY397FAK) expression patterns in both normal (n = 15) and EOPE (n = 15) placental tissues, including first trimester samples, using immunohistochemistry and Western blot techniques. Next, Y15 was used to inhibit FAK activity. CCK-8 detection, Western blotting, wound healing assay, Transwell assays and flow cytometry were employed to systematically evaluate FAK's impact on trophoblast cell line HTR8/SVneo. Through transcriptomic and bioinformatics analyses, we identified Rap1 as a potential downstream mediator of FAK signaling in trophoblasts. In a mouse model of preeclampsia, we found decreased expression of both FAK and Rap1 in placental tissues, supporting our in vitro findings. These results suggest that FAK may contribute to preeclampsia development by regulating trophoblast invasion and proliferation through the Rap1 signaling pathway. Our study provides insights into the molecular mechanisms underlying EOPE and identifies FAK as a potential therapeutic target for preeclampsia treatment.