Preeclampsia is a severe pregnancy complication in part due to insufficient implantation. This study aimed at elucidating the mechanism of action of dipeptidyl peptidase IV (DPPIV) in preeclampsia. Small activating RNAs (saRNA) were used to upregulate DPPIV expression in human trophoblast JAR cells. The DPPIV expression level was analyzed by real-time quantitative PCR and western blot and its activity was measured by luminescent protease assay. MMP-9 activity was analyzed by zymography and cell invasion by matrigel invasion assay. DPPIV expression level and activity was significantly increased by saRNA in JAR cells. DDPIV specific inhibitor diprotin A inhibited its activity at both basal and activated levels. DPPIV did not regulate MMP-9 expression but did repress MMP-9 activity. The invading ability of JAR cells was reduced by saRNA but increased by diprotin A. DPPIV might be responsible for the shallow implantation of the placenta due to its inhibition of the invading ability of extravillous trophoblasts, causing preeclampsia at later stage of pregnancy. KEY WORDS: preeclampsia, trophoblast, dipeptidyl peptidase IV, small activating RNA, cell invasion, diprotin APreeclampsia is a severe complication which affects 5-8% of pregnancies and contributes significantly to maternal and fetal morbidity and mortality (Steegers et al., 2010). Moreover, women with preeclampsia have an increased risk of developing cardiovascular disease later in life. Preeclampsia is thought to be resulted from a complex interplay between genetic and environmental factors. Family studies provides the evidence for the involvement of genetic factors, which have shown that daughters and sisters of preeclamptic women have a higher risk of preeclampsia (Nilsson et al., 2004). Moreover, the incidence of preeclampsia is also different among various ethnic groups (Steegers et al., 2010). Unfortunately, the precise etiology of preeclampsia remains unclear after decades of efforts.It is required for a blastocyst to implant into the uterine endometrium to form a functional placenta during the establishment of mammalian pregnancy. A functional placenta formation requires the 'extravillous trophoblast' (EVT) engrafting and remodeling uterine spiral arteries to create placental blood supply at the end of the first trimester (Burton et al., 2010). Shallow or inappropriate implantation and placentation may result in first trimester miscarriage, preeclampsia, and other obstetric complications (Aplin, 2010). The trophoblast invasion is regulated by local endometrial environment that endometrial stromal cells differentiate into decidual Int.
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