Activation of Villous Trophoblastic p38 and ERK1/2 Signaling Pathways in Preterm Preeclampsia and HELLP Syndrome

摘要: Preterm preeclampsia is associated with the failure of trophoblast invasion, placental hypoxic/ischemic injury and release toxic substances, which promote terminal pathway preeclampsia. In term preeclampsia, factors yet unknown trigger placenta to induce pathway. The contribution villous these pathologic events has not been fully elucidated. Here we aimed study how stress signaling pathways influence trophoblastic functions in various subforms Tissue microarrays (TMAs) were constructed from placentas obtained pregnant women following groups: 1–2) preterm (n = 8) or without 7) HELLP syndrome; 3) late-onset 8); 4–5) 5) 9) controls. TMA slides stained for phosphorylated Akt-1, ERK1/2, JNK, p38 kinases, immunostainings semi-quantitatively evaluated. BeWo cells kept conditions, expression FLT1, GCM1, LEP, PGF was profiled by qRT-PCR, while kinase activities measured phospho-kinase immunoassays. We found that: 1) Placental LEP FLT1 up-regulated syndrome compared controls; 2) Mean pp38 immunoscore higher especially cases syndrome, than pERK1/2 4) cells, ischemia expression, it increased JNK decreased ERK1/2 activity. Hypoxia down-regulated 6) IL-1β treatment had most impact on expression. conclusion, hypoxic ischemic stress, along factors, activates signaling, a key role functional changes activation may additional distinct mechanisms