HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia

Abstract

The HtrA serine peptidase 1 (HTRA1) is a multidomain secretory protein with serine–protease activity involved in the regulation of many cellular processes in both physiological and pathological conditions. HTRA1 is normally expressed in the human placenta, and its expression is higher in the first trimester compared to the third trimester, suggesting an important role of this serine protease in the early phases of human placenta development. The aim of this study was to evaluate the functional role of HTRA1 in in vitro models of human placenta in order to define the role of this serine protease in preeclampsia (PE). BeWo and HTR8/SVneo cells expressing HTRA1 were used as syncytiotrophoblast and cytotrophoblast models, respectively. Oxidative stress was induced by treating BeWo and HTR8/SVneo cells with H2O2 to mimic PE conditions in order to evaluate its effect on HTRA1 expression. In addition, HTRA1 overexpression and silencing experiments were performed to evaluate the effects on syncytialization, cell mobility, and invasion processes. Our main data showed that oxidative stress significantly increased HTRA1 expression in both BeWo and HTR8/SVneo cells. In addition, we demonstrated that HTRA1 has a pivotal role in cell motility and invasion processes. In particular, HTRA1 overexpression increased while HTRA1 silencing decreased cell motility and invasion in HTR8/SVneo cell model. In conclusion, our results suggest an important role of HTRA1 in regulating extravillous cytotrophoblast invasion and motility during the early stage of placentation in the first trimester of gestation, suggesting a key role of this serine protease in PE onset.

First Trimester Placental Biomarkers for Pregnancy Outcomes

“…They found that HTRA1 expression was increased in an oxidative stress condition, which is typical in women who developed late PE. Moreover, the HTRA1 contribution in cell migration and invasion was shown, underlining the possible role of HTRA1 in placental development and, consequently, in PE onset [ 101 ]. The correlation between this protein and adverse pregnancy outcomes has recently emerged.…”

Circulating miRNAs and Preeclampsia: From Implantation to Epigenetics

“…Reduced arterial compliance and peripheral vasoconstriction characterize the preeclamptic condition from the early stages [16]; however, the exact pathophysiology of preeclampsia is still unknown. Probably, the initial defect in placentation and vascularization in the placenta bed due to poor trophoblast invasion of the spiral arteries [17][18][19] leads to an inappropriate activation of the immune system [20], as it occurs in recurrent miscarriage [21]. It is known that oxidative stress and inflammation are involved in endothelial dysfunction [22][23][24][25][26][27], a key process underlying several diseases including preeclampsia [28][29][30][31][32].…”