ANXA4 promotes trophoblast invasion via the PI3K/AKT/eNOS pathway in preeclampsia

Objectives: The inadequate trophoblast invasion is associated with the development of preeclampsia (PE). Considering that annexin A4 (ANXA4) enhances tumor invasion, we aimed to explore the functional role of ANXA4 in trophoblast cells and to examine the underlying mechanism. Methods: ANXA4 expression in PE placentas was analyzed using immunohistochemistry and Western blot. Cell proliferation, invasion, and apoptosis were determined using MTT assay, Transwell assay, and flow cytometry, respectively. The expression levels of matrix metalloproteinase (MMP)‑2, MMP‑9, phosphoinositide 3‑kinase (PI3K), AKT, phosphorylated (p)‑AKT, and phosphorylated-endothelial nitric oxide synthase (p-eNOS) were detected by Western blot. Placentas were prepared for pathological examination using hematoxylin and eosin staining and apoptosis determination using TUNEL method. Results: Expression of ANXA4, PI3K, p-AKT and p-eNOS were downregulated in human PE placentas and PE placentas-derived extravillous cytotrophoblasts (EVCTs...