Background: Preeclampsia is an idiopathic disease that occurs during pregnancy. Recent studies have considered abnormal autophagy as a new pathogenesis for this disorder, while little is known about its underlying molecular mechanisms. Apoptosis-stimulating protein of p53-2 (ASPP2) is one of the apoptosis-stimulating of p53 protein family members which can regulate cellular autophagy.
Results: In this study, we found ASPP2 expression was remarkably increased in trophoblasts of placentas from preeclamptic pregnancies and the hypoxia-induced trophoblast cell lines HTR8/SVneo and JEG-3 cells; and expression of ASSP2 in placentas was positively correlated with systolic blood pressure, diastolic blood pressure and BMI of pregnancies. Functionally, ASPP2 promotes preeclampsia through enhancement of trophoblast autophagy via accelerating release of Beclin-1 from Bcl-2-Beclin-1 complexes. More importantly, we found that decrease of DNMT1 and G9a cooperatively reduced DNA methylation and H3K9me2 at ASPP2 promoter, while increased binding of E2F1 at ASPP2 promoter, leading to transcription activation of ASPP2 in preeclamptic trophoblasts.
Conclusions: Our study suggests ASPP2 might be a novel diagnostic and prognostic biomarker for preeclampsia.